Formulation for oral administration of non-naturally occurring melanocortin analogs for treating substance use disorders and / or modulating diabetes

Abstract

Provided herein are pharmaceutical compositions of non-naturally occurring melanocortin analogs formulated for oral administration. The non-naturally occurring melanocortin analogs may be partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.

Description

Docket No.: 183B-412978-WOFORMULATION FOR ORAL ADMINISTRATION OF NON-NATURALLY OCCURRING MELANOCORTIN ANALOGS FOR TREATING SUBSTANCE USE DISORDERS AND / OR MODULATING DIABETESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 759,024, filed February 14, 2025; U.S. Provisional Patent Application No. 63 / 759,023, filed February 14, 2025; U.S. Provisional Patent Application No. 63 / 759,020, filed February 14, 2025; U.S. Provisional Patent Application No. 63 / 759,025, filed February 14, 2025; and U.S. Provisional Patent Application No. 63 / 704,519, filed October 7, 2024, all of which are incorporated herein by reference in their entirety.INCORPORATION BY REFERENCE OF SEQUENCE LISTING

[0002] This application contains an ST.26 compliant Sequence Listing, which is submitted concurrently in xml format and is hereby incorporated by reference in its entirety. The .xml copy, created on October 03, 2025 is titled “183B-412978-WO_SL.xml” and is 1 ,108,510 bytes in size.BACKGROUND

[0003] Various routes of administration, including subcutaneous (SC), intravenous (IV), and oral, have been employed to deliver medications. Among these, oral administration may be preferred by both users and healthcare providers due to its non-invasive nature, ease of use, and patient compliance. Despite the availability of SC and IV administration routes, which may be effective in delivering certain medications, these require healthcare professional intervention or self-administration techniques that can cause discomfort, administration site irritation, and potential complications. In comparison, oral drug formulations may be advantageous over SC and IV by alleviating these issues.

[0004] As such, there is a need for oral drug formulations that leverage the benefits of oral administration over other routes, while simultaneously increasing bioavailability of such oral dug formulations.-1 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOSUMMARY

[0005] Provided herein are pharmaceutical compositions comprising non-naturally occurring melanocortin analogs for oral administration.

[0006] In one aspect, the present technology relates to an orally deliverable pharmaceutical composition comprising a non-naturally occurring melanocortin analog, the melanocortin analog comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);-2-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that:-3-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0007] In another aspect, the present technology relates to a pharmaceutical composition comprising a non-naturally occurring melanocortin agonist and a permeation enhancer, the non-naturally occurring melanocortin agonist comprising a sequence of Formula (I).

[0008] In another aspect, the present technology relates to a pharmaceutical composition for oral administration of a non-naturally occurring melanocortin agonist, the-4-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO composition comprising a permeation enhancer and a non-naturally occurring melanocortin analog comprising a sequence of Formula (I).

[0009] In yet another aspect, the present technology relates to a pharmaceutical composition formulated to deliver about 0.1 mg / kg to about 5 mg / kg, per body weight of a subject, of a non-naturally occurring melanocortin agonist to the subject, the pharmaceutical composition comprising a permeation enhancer; and a non-naturally occurring melanocortin agonist comprising a sequence of Formula (I).

[0010] Also provided herein are oral dosage units of the pharmaceutical compositions described herein and methods of administering the same.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIGS. 1A-1 H show plasma concentration in Male Sprague-Dawley (MSD) rats orally administered 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 2) formulations with and without permeation enhancers.

[0012] FIGS. 2A and 2B show maximum concentration (Cmax) (FIG. 2A) and area under the curve (AUG) values (FIG. 2B) of 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal- dPro-NH2; SEQ ID NO: 2) in rats orally administered 010 with and without permeation enhancers.

[0013] FIG. 3 shows oral bioavailability of 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp- Orn]-dVal-dPro-NH2; SEQ ID NO: 2) with increasing propyl gallate concentrations in rats (010 40 mg / kg), beagle dogs (010 10 mg / kg), and cynomolgus monkeys (010 5 mg / kg).

[0014] FIGS. 4A-4C show 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro- NH2; SEQ ID NO: 2) plasma concentrations in cynomolgus monkeys orally administered 5 mg / kg 010 in water (PO1 ) (FIG. 4A), 5 mg / kg 010 and 10 mg / kg propyl gallate in water (PO2) (FIG. 4B), or 5 mg / kg 010 and 30 mg / kg propyl gallate in water (PO3)(FIG. 4C).

[0015] FIG. 5 shows 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 2) cerebral spinal fluid (CSF) concentrations in cynomolgus monkeys orally administered the PO3 formulation of FIG. 10.-5-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0016] FIGS. 6A-6D show plasma concentrations of melanocortin agonists in cynomolgus monkeys orally administered A07D (Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]- dVal-dPro-NH2; SEQ ID NO: 3), 03 (Ac-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal- dPro-NH2; SEQ ID NO: 4), 07 (Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 5), and 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 2), at various concentrations. FIGS. 6B and 6C shows plasma concentrations in cynomolgus monkeys after oral administration of 10 mg / kg and 30 mg / kg 07 (FIG. 6B) and 03 (FIG. 6C). FIG. 6D shows plasma concentrations in cynomolgus monkeys after oral administration of 3 mg / kg, 10mg / kg, 30 mg / kg, and 60 mg / kg 010.DETAILED DESCRIPTION

[0017] Described herein are pharmaceutical compositions comprising non-naturally occurring melanocortin analogs formulated for oral administration to a subject. In order to achieve desired therapeutic outcomes, the pharmaceutical compositions are specifically formulated with one or more components useful for oral delivery of the non-naturally occurring melanocortin analog. The pharmaceutical compositions of the present technology and the one or more components thereof may be Generally Recognized as Safe (GRAS) under one or more conditions of the present technology. In some embodiments, the one or more components of the pharmaceutical composition are selected based on desirable pharmacokinetic properties. In further embodiments, the one or more components comprise a permeation enhancer, such as but not limited to, propyl gallate.

[0018] The following description is merely exemplary in nature and is not intended to limit the present technology, its applications, or its uses. It should be understood that throughout the drawings, corresponding reference numerals indicate like or corresponding parts and features. The description of specific examples indicated in various embodiments of the present technology are intended for purposes of illustration only and are not intended to limit the scope of the present technology disclosed herein. Moreover, recitation of multiple embodiments having stated features is not intended to exclude other embodiments having additional features or other embodiments incorporating different combinations of the stated features.-6-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0019] Furthermore, the detailed description of various embodiments herein makes reference to the accompanying drawing / FIGS, which show various embodiments by way of illustration. While the embodiments are described in sufficient detail to enable those skilled in the art to practice the present technology, it should be understood that other embodiments may be realized, and that logical changes may be made without departing from the spirit and scope of the present technology. Thus, the detailed description herein is presented for purposes of illustration only and not of limitation. For example, steps recited in any method or process, may be executed in any order and are not limited to the order presented. Moreover, any of the steps thereof may be outsourced to or performed by one or more third parties.Definitions

[0020] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present technology belongs. For the purposes of the present technology, the following terms are defined below.

[0021] The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0022] The term “about” means a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by acceptable levels in the art. Typically, such variation may be as much 10% above and below a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length and such variation may be influenced by standard applicable measurement practices. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth.

[0023] As used herein, “oral administration” and “orally deliverable” include any form of delivery of a non-naturally occurring melanocortin analog or a composition thereof to a subject wherein the non-naturally occurring melanocortin analog or the composition is placed in the mouth of the subject, whether or not the non-naturally occurring melanocortin-7-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO analog or composition is swallowed. Thus, “oral administration” includes buccal and sublingual, as well as esophageal administration.

[0024] The terms “active ingredient” and “active compound” refer to a biologically active substance, whether naturally or non-naturally occurring, that is the main component of the pharmaceutical composition which elicits the intended effect of an administered therapeutic. This can be any component that drives the pharmacological activity or direct effect in the diagnosis, cure, mitigation, treatment, or prevention of the conditions associated with the present technology.

[0025] The terms “composition,” “pharmaceutical composition,” “formulation,” and “pharmaceutical formulation” are used interchangeably herein to refer to a mixture of the active ingredient with one or more components, such as pharmaceutically acceptable carriers and / or excipients.

[0026] As used herein, a “pharmaceutically acceptable carrier” refers to a carrier or diluent that does not cause significant irritation to an organism, does not abrogate the biological activity and properties of the administered active ingredient, and / or does not interact in a deleterious manner with the other components of the composition in which it is contained. The term “carrier” encompasses any excipient, binder, diluent, filler, salt, buffer, solubilizer, lipid, stabilizer, or other material well known in the art for use in pharmaceutical formulations. The choice of a carrier for use in a composition will depend upon the intended route of administration for the composition. The preparation of pharmaceutically acceptable carriers and formulations containing these materials is described in, e.g., Remington's Pharmaceutical Sciences, 21 st Edition, ed. University of the Sciences in Philadelphia, Lippincott, Williams & Wilkins, Philadelphia Pa., 2005, which is incorporated herein by reference in its entirety).

[0027] As used herein, the terms “effective amount” or “therapeutically effective amount”, refer to that amount of the active ingredient being administered which will relieve to some extent one or more of the symptoms of the disease being treated. The result can be a reduction and / or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. An appropriate “effective amount” can differ-8-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO from one individual to another. An appropriate “effective amount” in any individual case can be determined using techniques, such as a dose escalation study.

[0028] The terms “subject” and “patient” refer to anyone being evaluated for disease or condition or being administered a therapeutic or pharmaceutical composition. This includes people without diagnosed or confirmed disease or condition. This also includes people with diagnosed or confirmed disease or condition.

[0029] The term “control subject,” as used herein, refers to any subject used as a basis for comparison to the subject (e.g., test subject). A control subject includes, but is not limited to, any subject who has not been administered the therapeutic or pharmaceutical composition (e.g., the non-naturally occurring melanocortin analog, a therapeutically effective amount of the non-naturally occurring melanocortin analog or a pharmaceutical composition thereof) or administered a placebo.

[0030] “Melanocortin analogs,” “melanocortin peptides,” and “melanocortins,” are used interchangeably and refer to melanocortin-receptor ligands, which are macromolecules containing at least one melanocortin pharmacophore. Melanocortin analogs are typically peptides that bind melanocortin receptors under physiological conditions. Melanocortin analogs include non-naturally occurring melanocortin peptides and truncated and / or modified versions of melanocortin full-length protein or peptides. For example, the full-length pro-opiomelanocortin protein (POMC), prior to proteolytic cleavage of “sub-peptides,” consists of 241 amino acids. Tissue-specific proteolytic cleavage of POMC yields peptides ranging in size from 13 amino acids to 76 amino acids. See Bicknell and Lawry, Encyclopedia of Stress, vol. 3, 257-265, Academic Press (2000). Synthesized, non- naturally occurring melanocortin analogs having increased melanocortin receptor activity as discussed herein are approximately 7-12 amino acids in size. Melanocortin analogs exhibit binding functionality with melanocortin receptors. In addition to peptides, the non-naturally occurring melanocortin analog s include small molecule analogs of melanocortin or portions thereof comprised of organic compounds, inorganic compounds, or combinations of peptide and small molecule — i.e., peptide mimetics, or various combinations thereof. “Melanocortin peptides” can be structurally similar and / or functionally similar to biological melanocortin proteins in their ability to bind melanocortin receptors. Further, the non-naturally occurring-9-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO melanocortin analog s generally contain the pharmacophore: His-Phe-Arg-Trp (SEQ ID NO: 1 ) or a modified version thereof, or a structural or functional peptide mimetic thereof.

[0031] A “pharmacophore” is the minimum set of amino acid residues necessary to achieve a physiological effect; or a small molecule that is (with respect to a receptor) a structural mimic of the amino acid residues required for binding to and activation of a receptor. His-Phe-Arg-Trp (SEQ ID NO: 1 ) and their analogs are the pharmacophore of melanocortin for the regulated physiological effect. Therefore, non-naturally occurring melanocortin pharmacophore analogs can be small peptides or organic molecules designed to mimic the appearance or function (including activation or deactivation of receptor activity) of the melanocortin pharmacophore core sequence peptide.

[0032] The terms “bind,” “binding,” “complex,” and “complexing,” refer to all types of physical and chemical binding, reactions, complexing, attraction, chelating and the like.

[0033] The “peptides” described herein can be (a) naturally occurring, (b) produced by chemical synthesis, (c) produced by recombinant DNA technology, (d) produced by biochemical or enzymatic fragmentation of larger molecules, (e) produced by methods resulting from a combination of methods (a) through (d) listed above, or (f) produced by any other means for producing peptides.

[0034] The term “peptide” as used herein includes any structure comprised of two or more amino acids, including chemical modifications and derivatives of amino acids. The amino acids forming all or a part of a peptide may be naturally occurring amino acids, stereoisomers and modifications of such amino acids, non-protein amino acids, post- translationally modified amino acids, enzymatically modified amino acids, constructs or structures designed to mimic amino acids, and the like, so that the term “peptide” includes pseudopeptides and peptidomimetics, including structures which have a non-peptidic backbone. The term “peptide” also includes dimers or multimers of peptides. A “manufactured” peptide includes a peptide produced by chemical synthesis, recombinant DNA technology, biochemical, or enzymatic fragmentation of larger molecules, combinations of the foregoing or, in general, made by any other method. The term “peptide” includes peptides containing a variable number of amino acid residues, optionally with non--10-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO amino acid residue groups at the N- and C-termini, such groups including acyl, acetyl, alkenyl, alkyl, N-alkyl, amine, or amide groups, among others.

[0035] By employing chemical synthesis, a useful means of production, it is possible to introduce various amino acids which do not naturally occur along the chain, modify the N- or C-terminus, and the like, thereby providing for improved stability and formulation, resistance to protease degradation, and the like.

[0036] “Amino acids” are molecules containing an amine group, a carboxylic acid group, and a side-chain that is specific to each amino acid. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen and have the generic formula H2N — CHR — COOH, wherein R represents a side chain group. The various a-amino acids differ in the side-chain moiety that is attached to the a-carbon. The “amino acids” of the present technology include the known naturally occurring protein amino acids, which are referred to by both their common three letter abbreviation and single letter abbreviation. See generally Synthetic Peptides: A User’s Guide, G. A. Grant, editor, W.H. Freeman & Co., New York (1992), the teachings of which are incorporated herein by reference, including the text and table set forth at pages 11 through 24. As set forth above, the term “amino acid” also includes stereoisomers and modifications of naturally occurring protein amino acids, nonprotein amino acids, post-translationally modified amino acids, enzymatically synthesized amino acids, derivatized amino acids, constructs or structures designed to mimic amino acids, and the like. Modified and unusual amino acids are described generally in Synthetic Peptides: A User’s Guide, supra; Hruby et al., Biochem. J. 268:249-262 (1990); and Toniolo, Int. J. Peptide Protein Res. 35:287-300 (1990); the teachings of all of which are incorporated herein by reference.

[0037] The phrase “amino acid side chain moiety” used herein, including as used in the specification and claims, includes any side chain of any amino acid, as the term “amino acid” is defined herein. This thus includes the side chain moiety present in naturally occurring amino acids. It further includes side chain moieties in modified naturally occurring amino acids, such as glycosylated amino acids. It further includes side chain moieties in stereoisomers and modifications of naturally occurring protein amino acids, non-protein amino acids, post-translationally modified amino acids, enzymatically synthesized amino-11 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO acids, derivatized amino acids, constructs, or structures designed to mimic amino acids, and the like. For example, the side chain moiety of any amino acid disclosed herein is included within the definition. A “derivative” of an amino acid side chain moiety is included within the definition of an amino acid side chain moiety.

[0038] The “derivative” of an amino acid side chain moiety includes any modification to or variation in any amino acid side chain moieties, including a modification of naturally occurring amino acid side chain moieties. By way of example, derivatives of amino acid side chain moieties include straight chain or branched, cyclic or noncyclic, substituted or unsubstituted, saturated or unsaturated, alkyl, aryl or aralkyl moieties.

[0039] In the peptides described herein, conventional amino acid residues have their conventional meaning as given in Chapter 2400, of the Manual of Patent Examining Procedure, 8th Ed. Thus, “Ala” is alanine; “Arg” is arginine; “Asn” is asparagine; “Asp” is aspartic acid; “Cys” is cysteine; “Gin” is glutamine; “Glu” is glutamic acid; “His” is histidine; “lie” is isoleucine; “Leu” is leucine; “Lys” is lysine; “Met” is methionine; “Phe” is phenylalanine; “Pro” is proline; “Ser” is serine; Thr is threonine; “Trp” is tryptophan; “Tyr” is tryosine; and “Vai” is valine. Unless otherwise indicated, all amino acids abbreviations represent either isomer, i.e., the L-isomer, the D-isomer, or combinations thereof can be used. Thus, for example, “L-Phe” or “IPhe” is L-phenylalanine; “D-Phe” or “dPhe” is D- phenylalanine; “D- / L-Phe” or “d / IPhe” is D-phenylalanine, L-phenylalanine, or combinations thereof; and “Phe” is D-phenylalanine, L-phenylalanine, or combinations thereof, and so on.

[0040] Non-standard amino acids included herein are: “Nle” is norleucine; “Orn” is ornithine; and “p(F)dPhe” is parafluoro-D-phenylalanine.

[0041] An alpha (oc)-amino acid has the generic formula H2N — CocHR — COOH, where R is a side chain moiety and the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (i.e., the oc-carbon). Other types of amino acids exist when the amino group is attached to a different carbon atom. For example, beta (p)-amino acids, the carbon atom to which the amino group is attached is separated from the carboxylate group by one carbon atom, Cp.-12-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0042] When p-amino acids are incorporated into peptides, two main types of p- peptides exist: those with the side chain residue, R, on the carbon next to the amine are called p3peptides and those with the side chain residue on the carbon next to the carbonyl group are called p2amino acids. Further, p-amino acids may adopt L- or D- stereochemistry. Unless otherwise indicated, all p-amino acid abbreviations represent either isomer, i.e., the L-isomer, the D-isomer, or combinations thereof.

[0043] Gamma (y)-amino acids are amino acids with the carbon atom to which the amino group attaches is separated from the carboxylate moiety by two carbon atoms.

[0044] For additional modified and unusual amino acids, see §2422 of the MPEP, particularly Table 4 at 2400-24. Additionally, “Ac” indicates N-acetyl and “cyclo” refers to a cyclic structure, which is also shown in the literature as “c” or referred to as a “lactam.” “NH2” indicates an amine group, typically added on the C-terminus of a polypeptide. Accordingly, as used herein, an — NH2 moiety on the C-terminus of a peptide indicates an amidated C- terminus.

[0045] The term “acyl” includes a group RCO — , where R is an organic group. An example is the acetyl group CH3CO — , referred to herein as “Ac.”

[0046] A peptide is “acylated” when an alkyl or substituted alkyl group as defined above is bonded through one or more carbonyl { — (C=O) — } groups. A peptide is most usually acylated at the N-terminus.

[0047] An “amine” includes compounds that contain an amine group ( — NH2).

[0048] An “amide” includes compounds that have a trivalent nitrogen attached to a carbonyl group (i.e., — CO — NH2), such as for example methylamide, ethylamide, propylamide, and the like. A peptide is most usually amidated at the C-terminus by the addition of an amine ( — NH2) moiety to the C-terminal carboxyl group.

[0049] Amino acids, including stereoisomers and modifications of naturally occurring amino acids, protein amino acids, non-protein amino acids, post-translationally modified amino acids, enzymatically synthesized amino acids, derivatized amino acids, constructs, or structures designed to mimic amino acids (peptide mimetics), and the like, including all of the foregoing, are sometimes referred to herein as “residues.”-13-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0050] A peptide or amino acid “mimetic” is a non-amino acid molecule that mimics a peptide (a chain of amino acids) or one amino acid residue.

[0051] The disclosure of all publications, patents, and published patent applications listed herein are hereby incorporated by reference in their entireties, including but not limited to U.S. Patent Nos. 8,541 ,545 and 9,534,018 and PCT Publication No. WO 2025 / 123059.Pharmaceutical Compositions

[0052] The present technology provides pharmaceutical compositions comprising a non-naturally occurring melanocortin analog, wherein the composition is formulated for oral administration to a subject. In some embodiments, the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers and / or excipients. In some embodiments, the pharmaceutical composition comprises a permeation enhancer. Pharmaceutical compositions comprising a melanocortin analog and a permeation enhancer may have increased oral bioavailability compared to pharmaceutical compositions not comprising a permeation enhancer.

[0053] Pharmaceutical compositions of the present technology include a non-naturally occurring melanocortin analog as the active ingredient. Non-naturally occurring melanocortin analogs described herein may be selective for the melanocortin 4 receptor and / or melanocortin 3 receptor over other melanocortin receptors, i.e., the melanocortin 1 , melanocortin 2, and melanocortin 5 receptors. Some of the melanocortin analogs bind the melanocortin 4 receptor with greater affinity than the melanocortin 3 receptor. Certain melanocortin analogs bind the melanocortin 3 receptor with the same or generally similar affinity as the melanocortin 4 receptor.

[0054] The non-naturally occurring melanocortin analogs of the present technology may be full agonists for one or more melanocortin receptors. A full agonist may comprise a non-naturally occurring melanocortin analog having a maximum effect (Emax) agonist value of greater than or equal to 80%.

[0055] The non-naturally occurring melanocortin analogs of the present technology may be partial agonists or partial antagonists of one or more melanocortin receptor. A partial-14-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO agonist or antagonist may comprise a non-naturally occurring melanocortin analog having a maximum effect Emax agonist value of less than 80%.

[0056] If a non-naturally occurring melanocortin analog’s Emax agonist value is greater than it’s Emax antagonist value, then the non-naturally occurring melanocortin analog may be classified as an agonist (e.g., a full agonist or a partial agonist). Similarly, if a non-naturally occurring melanocortin analog’s Emax antagonist value is greater than it’s Emax agonist value, then the non-naturally occurring melanocortin analog may be classified as an antagonist (e.g., a full antagonist or a partial antagonist).

[0057] The non-naturally occurring melanocortin analogs of the present technology may be one or more of (i) a full MC4R agonist and a partial MC3R agonist; (ii) a full MC4R agonist and a partial MC3R antagonist; (iii) a full MC4R agonist having no MC3R agonist or antagonist activity; (iv) a partial MC4R agonist and a partial MC3R antagonist; or (v) a partial MC4R agonist having no MC3R agonist or antagonist activity.

[0058] The non-naturally occurring melanocortin analogs in accordance with the present technology may have structural features that impart specific properties on the analogs, such as, for example, degradation resistance, enhanced epithelial, gastrointestinal, and / or blood brain barrier transport, and binding affinity for the MC4R and / or MC3R. For example, in some embodiments, the non-naturally occurring melanocortin analogs comprise one or more of (i) blood brain barrier passage capabilities, (ii) enhanced epithelial and / or gastrointestinal transport; (iii) degradation resistance; or (iv) equipotency on MC3R and MC4R activity. In some embodiments, the non-naturally occurring melanocortin analogs comprise two or more of (i)-(iv). In some embodiments, the non-naturally occurring melanocortin analogs comprise each of (i)-(iv). Accordingly, in some embodiments, the melanocortin analogs include a stabilizing N-terminus, and / or a C-terminus that provides enhanced transport of the analog. In some embodiments, melanocortin analogs include a D-valine-D-proline (dVal-dPro) chain as their C-terminus, which may provide enhanced transport and resistance to degradation Additionally, in some embodiments, the melanocortin analogs have one or more beta hairpin (p-hairpin) and / or beta turn (p-turn) structures. In general, cyclization and D-amino acids may induce and / or stabilize beta-turns..-15-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0059] The presence of certain structural features may impart the non-naturally occurring melanocortin analogs of the present technology with specific binding properties. For example, inclusion of p(F)dPhe or dPhe at the R4position may result in enhanced binding and activation of the melanocortin 4 receptor. Accordingly, melanocortin analogs having p(F)dPhe or dPhe at R4may be full agonists on MC4R. Further, inclusion of Pro at the R3position may result in partial agonism of the melanocortin 3 receptor, whereas inclusion of His at the R3position may result in full agonism of the melanocortin 3 receptor.

[0060] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (I),X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic-16-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and-17-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0061] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (I), wherein:X1is absent or norlecuine (Nle);-18-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOX2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp,-19-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOD-hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-dPhe-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 6);Ac-Nle-c[Asp-dTyr-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 7);Ac-Nle-c[Asp-dGln-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 8);Ac-Nle-c[Asp-dTrp-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 9);Ac-Nle-c[Asp-Phe-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 10);Ac-Nle-c[Asp-Bip-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 11 );Ac-Nle-c[Asp-Trp-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 12);-20-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Tyr-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 13);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 14);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 15);Ac-Nle-c[Glu-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 16);Ac-Nle-c[Asp-dHis-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 17);Ac-Nle-c[Asp-Gln-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 18);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 19);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-NH2(SEQ ID NO: 20);Ac-Nle-c[Asp-Pro-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 21 );Ac-Arg-c[Asp-Pro-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 22);Ac-Nle-c[Asp-Trp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 23);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 24);Ac-Nle-c[Glu-Pro-p(CI)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 25);Ac-Ala-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 26);Ac-Ala-c[Glu-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 27);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 28);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 29);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 30);Ac-dAla-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 31 );Ac-Ala-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 32);Ac-Ala-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 33);Ac-Nle-c[Glu-Trp-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 34);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 35);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 36);-21 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-p(CI)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 37);Ac-Nle-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 38);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 39);Ac-Nle-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 38);Ac-Arg-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 40);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 41 );Ac-Nle-c[Glu-His-p(CI)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 42);Ac-Nle-c[Cys-His-p(CI)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 43);Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 44);Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 45);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 46);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 47);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 5);Ac-Nle-c[Asp-dTyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 48);Ac-Nle-c[Asp-dPhe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 49);Ac-Nle-c[Asp-dTrp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 50);Ac-Nle-c[Asp-Trp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 51 );Ac-Nle-c[Asp-Tyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 52);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 2);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);-22-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 60);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 61 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-Trp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 74);Ac-Nle-c[Glu-Trp-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 75);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 76);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 77);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 78);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 79);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 80);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 81 );-23-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 82);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 83);Ac-dOrn-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 84);Ac-dPhe-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 85);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 86);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 89);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 90);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-dAla-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 94);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 95);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97);Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2(SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2(SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2(SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);-24-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1 ')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2(SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2(SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-dHis-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 120);Ac-Nle-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 121 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 124);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);-25-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 142);Ac-Arg-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 143);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 144);Ac-Lys-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 145);Ac-His-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 146);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 149);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 150);-26-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 151 );Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.

[0062] In some embodiments of the sequence of Formula (I), R4is dPhe or p(F)dPhe. Accordingly, in some embodiments, the sequence of Formula (I) is a sequence of Formula (IA):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A) , wherein:-27-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOX1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp,-28-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOD-hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated,-29-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0063] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one-30-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO(Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and-31 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0064] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys),-32-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;-33-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-dTyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 48);Ac-Nle-c[Asp-dPhe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 49);Ac-Nle-c[Asp-dTrp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 50);Ac-Nle-c[Asp-Trp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 51 );Ac-Nle-c[Asp-Tyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 52);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);-34-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 60);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 61 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-Trp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 74);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 76);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 78);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 80);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 81 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 82);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 83);Ac-dOrn-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 84);Ac-dPhe-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 85);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);-35-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 89);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 90);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-dAla-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 94);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 95);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97);Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2(SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2(SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2(SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1 ')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );-36-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2(SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2(SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-dHis-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 120);Ac-Nle-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 121 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 124);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);Ac-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);-37-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2 (SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 142);Ac-Arg-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 143);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 144);Ac-Lys-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 145);Ac-His-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 146);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 149);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 150);Ac-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 151 );Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);-38-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2 (SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2 (SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.

[0065] In some embodiments of the sequence of Formula (I) or (IA), R4is dPhe. Accordingly, in some embodiments, the sequence of Formula (I) or (IA) is a sequence of Formula (IA(i)):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A(i)) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);-39-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanylhistidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp- Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe- Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4- amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine- 4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;-40-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0066] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA(i)):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A(i ) ) ,-41 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanylhistidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp- Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe- Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4- amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine- 4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp,-42-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOD-hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is-43-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOLys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0067] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA(i)), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanylhistidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp- Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe- Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4- amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine- 4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));-44-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);-45-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WONle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2 (SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2 (SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2 (SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2 (SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2 (SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2 (SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 124);-46-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);Ac-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 142);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 144);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 149);-47-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 150);Ac-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 151 );Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.

[0068] In some embodiments of the sequence of any one of Formulae (l)-(IA(i)), R3is Pro. Accordingly, in some embodiments, the sequence of any one of Formulae (l)-(IA(i)) is a sequence of Formula (X1-X2-X3- R-48-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO wherein:X1is absent or norlecuine (Nle);X2is absent or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is proline (Pro);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), and 2’-naphthylalanine (Nal(2’));R7is selected from the group consisting of glycine (Gly), Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, Ala, D-alanine (dAla), Gly, Hyp, D- hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D-threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and-49-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7or R8is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R1is Nle, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R1is not Nle, then the C-terminus is amidated, wherein when R1is Phe, dPhe, or Trp, then the N-terminus is not acetylated, and when R1is dAla, then Y2is dPro, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0069] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA(ii)) :X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8- Y1-Y2- Y3- Y4- Y5-Y6- Y7( I A ( i i ) ) , wherein:X1is absent or norlecuine (Nle);X2is absent or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);-50-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is proline (Pro);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), and 2’-naphthylalanine (Nal(2’));R7is selected from the group consisting of glycine (Gly), Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, Ala, D-alanine (dAla), Gly, Hyp, D- hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D-threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7or R8is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and-51 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R1is Nle, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R1is not Nle, then the C-terminus is amidated, wherein when R1is Phe, dPhe, or Trp, then the N-terminus is not acetylated, and when R1is dAla, then Y2is dPro, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0070] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA(ii)), wherein:X1is absent or norlecuine (Nle);X2is absent or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is proline (Pro);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), and 2’-naphthylalanine (Nal(2’));R7is selected from the group consisting of glycine (Gly), Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;-52-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, Ala, D-alanine (dAla), Gly, Hyp, D- hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D-threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7or R8is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2(SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2(SEQ ID NO: 103);-53-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2 (SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 109);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 162); andAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 163), wherein c represents cyclization through a lactam or disulfide bond.

[0071] Alternatively, in some embodiments of the sequence of any one of Formulae (I)- ( I A(i)) , R3is an amino acid other than Pro. In further embodiments, X3and Y5-Y7are absent. Accordingly, in some embodiments, the sequence of any one of Formulae (l)-(IA(i)) is a sequence of Formula (I A(iii)) :X1-X2- R1- R2- R3- R4- R5- R6- R7- R8-Y1- Y2- Y3-Y4( I A(i i i ) ) , wherein:-54-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOX1is absent or norlecuine (Nle);X2is absent or phenylalanine (Phe);R1is selected from the group consisting of Nle, Phe, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxy proline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8- dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6- tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 - amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of Pro, Lys, and Cys; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), D-tertleucine (dTle), dArg, dLys, and dLeu;Y2is absent or selected from the group consisting of dVal, dPro, and dHyp;Y3is absent or dVal;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys;-55-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R3is His, then R1is Nle, and either (i) R7is Pro or (ii) R5is transPro(guan) or cisPro(guan), and when R3is Hyp, then R7is not Pro.

[0072] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA(iii)) :X1-X2- R1- R2- R3- R4- R5- R6- R7- R8-Y1- Y2- Y3-Y4( I A(i i i ) ) , wherein:X1is absent or norlecuine (Nle);X2is absent or phenylalanine (Phe);R1is selected from the group consisting of Nle, Phe, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxy proline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8- dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6- tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 - amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);-56-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR4is dPhe;R5is selected from the group consisting of Arg, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of Pro, Lys, and Cys; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), D-tertleucine (dTle), dArg, dLys, and dLeu;Y2is absent or selected from the group consisting of dVal, dPro, and dHyp;Y3is absent or dVal;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R3is His, then R1is Nle, and either (i) R7is Pro or (ii) R5is transPro(guan) or cisPro(guan), and when R3is Hyp, then R7is not Pro.

[0073] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA(iii)), wherein:X1is absent or norlecuine (Nle);X2is absent or phenylalanine (Phe);R1is selected from the group consisting of Nle, Phe, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);-57-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxy proline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8- dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6- tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 - amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of Pro, Lys, and Cys; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), D-tertleucine (dTle), dArg, dLys, and dLeu;Y2is absent or selected from the group consisting of dVal, dPro, and dHyp;Y3is absent or dVal;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and-58-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 115);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 142);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 144);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam bond.-59-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0074] In some embodiments of the sequence of Formula (I) or (I A), R4is p(F)dPhe. In further embodiments, X2, X3, R8, and Y4-Y7are absent. Accordingly, in some embodiments, the sequence of Formula (I) or (IA) is a sequence of Formula (IB):X1- R1- R2- R3- R4- R5- R6- R7-Y1-Y2-Y3(IB), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, phenylalanine (Phe), proline (Pro), biphenylalanine (Bip), glutamine (Gin), and D-glutamine (dGIn);R4is para-fluoro-D-phenylalanine (p(F)dPhe);R5is Arg or His;R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of, Lys, Orn, Cys, and dCys,Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is dVal or dPro;Y3is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys, or Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys; provided that: when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R2is not Cys, R6is Trp, and the C-terminus is amidated.-60-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0075] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IB):X1- R1- R2- R3- R4- R5- R6- R7-Y1-Y2-Y3(IB), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, phenylalanine (Phe), proline (Pro), biphenylalanine (Bip), glutamine (Gin), and D-glutamine (dGIn);R4is para-fluoro-D-phenylalanine (p(F)dPhe);R5is Arg or His;R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of, Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is dVal or dPro;Y3is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys, or Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that: when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R2is not Cys, R6is Trp, and the C-terminus is amidated.-61 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0076] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IB), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, phenylalanine (Phe), proline (Pro), biphenylalanine (Bip), glutamine (Gin), and D-glutamine (dGIn);R4is para-fluoro-D-phenylalanine (p(F)dPhe);R5is Arg or His;R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of, Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is dVal or dPro;Y3is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys, or Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);-62-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96); andAc-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97), wherein c represents cyclization through a lactam or disulfide bond.-63-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0077] In some embodiments of the sequence of Formula (I), R4is p(CI)dPhe. In further embodiments, X2, X3, R8, and Y5-Y7are absent. Accordingly, in some embodiments, the sequence of Formula (I) is a sequence of Formula (IC):X1- R1- R2- R3- R4- R5- R6- R7- Y1- Y2-Y3- Y4( I C) , wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), glutamic acid (Glu), and D-cysteine (dCys);R3is selected from the group consisting of His, 4-amino-1 ,2,4,5-tetrahydro-2- benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)- one (Ata), and 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia);R4is para-chloro-D-phenylalanine (p(CI)dPhe);R5is Arg;R6is Trp;R7is selected from the group consisting of Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is selected from the group consisting of dVal, dPro, and dTle;Y3is absent, dVal, or dPro;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that: when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle.-64-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0078] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IC):X1- R1- R2- R3- R4- R5- R6- R7-Y1-Y2-Y3-Y4( I C) , wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), glutamic acid (Glu), and D-cysteine (dCys);R3is selected from the group consisting of His, 4-amino-1 ,2,4,5-tetrahydro-2- benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)- one (Ata), and 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia);R4is para-chloro-D-phenylalanine (p(CI)dPhe);R5is Arg;R6is Trp;R7is selected from the group consisting of Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is selected from the group consisting of dVal, dPro, and dTle;Y3is absent, dVal, or dPro;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that: when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle.-65-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0079] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of Formula (IC), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), glutamic acid (Glu), and D-cysteine (dCys);R3is selected from the group consisting of His, 4-amino-1 ,2,4,5-tetrahydro-2- benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)- one (Ata), and 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia);R4is para-chloro-D-phenylalanine (p(CI)dPhe);R5is Arg;R6is Trp;R7is selected from the group consisting of Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is selected from the group consisting of dVal, dPro, and dTle;Y3is absent, dVal, or dPro;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 44);Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 45);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 46); andAc-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 47),-66-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO wherein c represents cyclization through a lactam or disulfide bond.

[0080] In some embodiments, the non-naturally occurring melanocortin analog has one or more beta hairpin (p-hairpin) and / or beta turn (p-turn) structures. In some embodiments, the presence of Pro, dPro, Hyp, dHyp, transPro(guan), and / or c / sPro(guan), provides the p- hairpin and / or p-turn structures of the non-naturally occurring melanocortin analog. In some embodiments, the disulfide bond of the sequence of any one of Formulae (l)-(IC), if present, provides the p-hairpin and / or p-turn structures of the non-naturally occurring melanocortin analog.

[0081] As will be appreciated by the skilled artisan, non-naturally occurring melanocortin analogs comprising a sequence of any one of Formulae (l)-(IC), have an N- terminus and a C-terminus. The melanocortin analogs of the present technology are written beginning with the N-terminus at the left-most amino acid residue and ending with the C- terminus at the right most residue. Accordingly, the N-terminus of a non-naturally melanocortin analog comprising a sequence of any one of Formulae (l)-(IC) may be at any of X1, X2, X3, and R1. Analogously, the C-terminus of a non-naturally occurring melanocortin analog comprising a sequence of any one of Formulae (l)-(IC) may be at any of R7, R8, Y1, Y2, Y3, Y4, Y5, Y6, and Y7.

[0082] In some embodiments, the N-terminus of the non-naturally occurring melanocortin analog is modified by an acyl group. In some embodiments, the acyl group is acetyl group

[0083] In some embodiments, the N-terminus of the non-naturally occurring melanocortin analog is not modified.

[0084] As discussed above, Y1Y2Y3Y4Y5Y6Y7represents a C-terminus of the non- naturally occurring melanocortin analog. In some embodiments, Y1-Y7are absent. In some embodiments, Y1is present and Y2-Y7are absent. In some embodiments, Y1and Y2are present and Y3-Y7are absent. In some embodiments, Y1-Y3are present and Y4-Y7are absent. In some embodiments, Y1-Y4are present and Y5-Y7are absent. In some-67-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO embodiments, Y1-Y5are present and Y6-Y7are absent. In some embodiments, Y1-Y6are present and Y7is absent. In some embodiments, Y1-Y7are present.

[0085] In some embodiments, the C-terminus of the non-naturally occurring melanocortin analog is modified by an amide groupthe sequence of any one of Formulae (l)-(IC), a non-naturally occurring melanocortin analog with a C- terminus modified by an amide may be represented by a terminal -NH2.

[0086] In some embodiments, the C-terminus of the non-naturally occurring melanocortin analog is not modified. In the sequence of any one of Formulae (l)-(IC), a non- naturally occurring melanocortin analog with an unmodified C-terminus may be represented by -OH.

[0087] Non-naturally occurring melanocortin analogs comprising a sequence of any one of Formulae (l)-(IC) are cyclized. For example, the non-naturally occurring melanocortin analog may be cyclized through a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen.

[0088] In some embodiments, the non-naturally occurring melanocortin analog is cyclized through a lactam bond. In some embodiments, the sequence of any one of Formulae (l)-(IC) is cyclized through a lactam bond between R2and R7. In some embodiments, the sequence of any one of Formulae (l)-(IC) is cyclized through a lactam bond between R2and R8.

[0089] In some embodiments of the sequence of any one of Formulae (l)-(IC), R4is Phe. In further embodiments, R1is Nle, R2is Asp, R3is Pro or Pro-His, R5is Arg, R6is Trp,-68-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO and R7is Lys. In some embodiments, Y1is dVal and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is:Ac-Nle-c[Asp-Pro-Phe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 169); orAc-Nle-c[Asp-Pro-His-Phe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 170), wherein c represents cyclization through R2and R7via a lactam bond.

[0090] In some embodiments of the sequence of any one of Formulae (l)-(IC), R4is dPhe or p(F)dPhe. In further embodiments, R1is Nle, R2is Asp or Glu, R3is Pro, R5is Arg, R6is Trp, and R7is Lys or Orn. In some embodiments, Y1is dVal and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 171 );Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 172);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(A07D; SEQ ID NO: 3);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 174);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 175); andAc-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 176), wherein c represents cyclization through R2and R7via a lactam bond.

[0091] In some embodiments of the sequence of any one of Formulae (l)-(IC), R1is Nle. Alternatively, in some embodiments, R1is an amino acid other than Nle. In further embodiments, R4is dPhe. In some embodiments, R1is selected from dLeu, dAla, Ala, dArg, Arg, dTyr, dLys, Lys, dHis, His, dOrn, Orn, Phe, dPhe, Trp, and dTrp. In further embodiments, R2is Asp, R3is Pro, R5is Arg, R6is Trp, R7is Lys. In still further embodiments, Y1is dVal and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-dLeu-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 177);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 178);-69-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Ala-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 179);Ac-dArg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 180);Ac-dTyr-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 181 );Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 182);His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 183);Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 184); dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 185); dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 186); dTrp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 187);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 188);Ac-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 189);Ac-Lys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 190);Ac-His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 191 );Ac-dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 192);Ac-Orn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 193); andAc-dOrn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 194), wherein c represents cyclization through R2and R7via a lactam bond.

[0092] In some embodiments, R4is dPhe and R1is selected from Ala, dArg, Arg, dLys, Lys, dHis, His, dOrn, and Orn. In further embodiments, R2is Asp, R3is Pro, R5is Arg, R6is Trp, R7is Lys. In still further embodiments, Y1is dTle and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Ala-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 195);Ac-dArg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 196);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 197);Ac-Lys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 198);-70-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 199);Ac-His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 200);Ac-dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 201 ); andAc-Orn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 202), wherein c represents cyclization through R2and R7via a lactam bond.

[0093] Alternatively, in some embodiments, Y1is an amino acid other than dTle or dVal and / or Y2is an amino acid other than dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dVal-dPro-NH2 (SEQ ID NO: 203);Ac-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2 (03; SEQ ID NO: 4);Ac-Lys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dPro-NH2 (SEQ ID NO: 204);Ac-His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2 (SEQ ID NO: 205);Ac-dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2 (SEQ ID NO: 206); andAc-dOrn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 207), wherein c represents cyclization through R2and R7via a lactam bond.

[0094] In some embodiments, R1is an amino acid other than Nle and R4is p(F)dPhe. In some embodiments, R1is selected from Ala, dArg, Arg, dLys, Lys, dHis, and His. In further embodiments, R3is Pro. In still further embodiments, R2is Asp, R5is Arg, R6is Trp, R7is Lys. In some embodiments, Y1is dVal and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Ala-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 208);Ac-dArg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 209);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 210);Ac-Lys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 211 );Ac-dLys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 212);-71 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-His-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 213); andAc-dHis-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 214), wherein c represents cyclization through R2and R7via a lactam bond.

[0095] Alternatively, in some embodiments, Y1is dTle and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Ala-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 215);Ac-dArg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 216);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 217);Ac-Lys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 218);Ac-dLys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 219);Ac-His-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 220); andAc-dHis-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 221 ), wherein c represents cyclization through R2and R7via a lactam bond.

[0096] In some embodiments, R4is p(F)dPhe and R3is His. In further embodiments, R2is Asp, R5is Arg, R6is Trp, R7is Lys. In still further embodiments, Y1is dVal or dTle and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Ala-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 222);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 223); andAc-Ala-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 224), wherein c represents cyclization through R2and R7via a lactam bond.

[0097] In some embodiments, R1is an amino acid other than Nle and R4is p(CI)dPhe. In further embodiments, R1is selected from dArg, Arg, dLys, Lys, dHis, and His. In further embodiments, R2is Asp, R3is His, R5is Arg, R6is Trp, R7is Lys. In some embodiments,-72-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY1is dVal and Y2is dPro. In some embodiments, the sequence of any one of Formulae (I)- (IC) is selected from the group consisting of:Ac-Arg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 225);Ac-Lys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 226);Ac-dLys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 227);Ac-His-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 228); andAc-dHis-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 229), wherein c represents cyclization through R2and R7via a lactam bond.

[0098] Alternatively, in some embodiments, Y1is dTle and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 230);Ac-Arg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 231 );Ac-Lys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 232);Ac-dLys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 233);Ac-His-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 234); andAc-dHis-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 235), wherein c represents cyclization through R2and R7via a lactam bond.

[0099] In some embodiments of the sequence of any one of Formulae (l)-(IC), R3is Pro or His. Alternatively, in some embodiments, R3is an amino acid other than Pro or His. In further embodiments, R4is dPhe. In some embodiments, R3is selected from Ala, Leu, Hyp, Phe, dPhe, Bip, dGIn, Trp, dTrp, loc, Tic, Aba, Aia, Ata, Ate, APC, or APPC. In some embodiments, R1is Nle, R2is Asp, R5is Arg, R6is Trp, R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-loc-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 236);Ac-Nle-c[Asp-Aba-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 237);-73-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Aia-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 238);Ac-Nle-c[Asp-Ata-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 239);Ac-Nle-c[Asp-APC-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 240);Ac-Nle-c[Asp-APPC-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 241 );Ac-Nle-c[Asp-Ala-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 242);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 243);Ac-Nle-c[Asp-dPhe-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 244);Ac-Nle-c[Asp-dGln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 245);Ac-Nle-c[Asp-Trp-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 246);Ac-Nle-c[Asp-dTrp-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 247);Ac-Nle-c[Asp-Tyr-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 248);Ac-Nle-c[Asp-dTyr-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 249);Ac-Nle-c[Asp-Atc-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 250);Ac-Nle-c[Asp-Leu-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 251 );Ac-Nle-c[Asp-Tic-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 252);Ac-Nle-c[Asp-Phe-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 253); andAc-Nle-c[Asp-Bip-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 254), wherein c represents cyclization through R2and R7via a lactam bond.

[0100] In some embodiments, R3is an amino acid other than Pro or His and R4is p(F)dPhe. In some embodiments, R3is selected from Gin, dGIn, dHis, Phe, and Bip. In some embodiments, R1is Nle, R2is Asp, R5is Arg, R6is Trp, R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Gln-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 255);Ac-Nle-c[Asp-dGln-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 256);-74-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-dHis-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 257);Ac-Nle-c[Asp-Phe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 258); andAc-Nle-c[Asp-Bip-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 259), wherein c represents cyclization through R2and R7via a lactam bond.

[0101] In some embodiments, R3is an amino acid other than Pro or His and R4is p(CI)dPhe. In some embodiments, R3is selected from Aba, Aia, and Ata. In some embodiments, R1is Nle, R2is Asp, R5is Arg, R6is Trp, R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Aba-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 260);Ac-Nle-c[Asp-Aia-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 261 ); andAc-Nle-c[Asp-Ata-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 262), wherein c represents cyclization through R2and R7via a lactam bond.

[0102] In some embodiments, R3is a dipeptide. In further embodiments, R4is dPhe. In some embodiments, R3is a dipeptide comprising His. In further embodiments, R3is Ala- His. In further embodiments, X1is Nle, Arg, or dArg, R5is Arg, R6is Trp, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Ala-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 263);Ac-Arg-c[Asp-Ala-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 264); andAc-dArg-c[Asp-Ala-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 265), wherein c represents cyclization through R2and R7via a lactam bond.

[0103] In some embodiments, R3is Pro-His. In further embodiments, R1is Nle, R5is Arg, R6is Trp, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is: Ac-Nle-c[Asp-Pro-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 266), wherein c represents cyclization through R2and R7via a lactam bond.-75-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0104] In some embodiments, R3is Phe-His. In further embodiments, R1is Nle, R5is Arg, R6is Trp, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 267);Ac-Nle-Phe-Phe-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 268);Ac-Nle-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dLeu-dPro-NH2 (SEQ ID NO: 269); andAc-Nle-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 270), wherein c represent cyclization through R2and R7via a lactam bond.

[0105] In some embodiments, R4is dPhe and R3is a dipeptide comprising Pro. In further embodiments, R3is Trp-Pro. In still further embodiments, R5is Arg, R6is Trp, Nal(2’), or dNal(2’), and R7is Lys. In some embodiments, R1is Nle, Y1is dVal, and Y2is dPro. In some embodiments, R1is an amino acid other than Nle. In some embodiments, Y1is an amino acid other than dVal and / or Y2is an amino acid other than dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 271 );Ac-Nle-c[Cys-Trp-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 272);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 273);Ac-Ala-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 274);Ac-Lys-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 275);Ac-dLys-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 276);Ac-Arg-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 277);Ac-dArg-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 278);Ac-dHis-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 279);Ac-His-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 280);Ac-Nle-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 281 );-76-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dArg-dVal-dPro-NH2 (SEQ ID NO: 282);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2 (SEQ ID NO: 283);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dArg-dPro-NH2 (SEQ ID NO: 284);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2 (SEQ ID NO: 285);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2 (SEQ ID NO: 286);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 287);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 288);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 289); andAc-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 290), wherein c represents cyclization through R2and R7via a lactam or disulfide bond.

[0106] In further embodiments, R3is a derivative of Trp-Pro. Derivatives of Trp-Pro may include substitution of Trp for another aromatic amino acid or substitution of Pro for another aliphatic amino acid. In some embodiments, R3is selected from Trp-Ala, Trp-Leu, Tyr-Pro, dTyr-Pro, ad dPhe-Pro. In further embodiments, R5is Arg, R6is Trp, and R7is Lys. In still further embodiments, R1is Nle, Y1is dVal, and Y2is dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Trp-Ala-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 291 );Ac-Nle-c[Asp-Trp-Leu-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 292);Ac-Nle-c[Asp-Tyr-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 293);Ac-Nle-c[Asp-dPhe-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 294); andAc-Nle-c[Asp-dTyr-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 295), wherein c represents cyclization through R2and R7via a lactam bond.

[0107] In some embodiments of the sequence of any one of Formulae (l)-(IC), R3is Pro. In further embodiments, R4is dPhe or p(F)dPhe.

[0108] In some embodiments, R3is Pro and the sequence of any one of Formulae (I)- (IC) is cyclized through R2and R7. In some embodiments, the sequence of any one of-77-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOFormulae (l)-(IC) is cyclized through R2and R7, and R2is Asp and R7is Lys. Alternatively, in some embodiments, R2is an amino acid capable of forming a linkage to the residue at R7other than Asp and / or R7is an amino acid capable of forming a linkage to the residue at R2other than Lys. For example, when R2is an amino acid other than Asp and / or R7is an amino acid other than Lys, the residue at R2may be capable of forming a linkage such as a lactam bond or a disulfide bond with the residue at R7. In some embodiments, R2is Asp or Glu and R7is Orn, and the peptide is cyclized through R2and R7via a lactam bond.

[0109] In some embodiments, R2and R7are each independently Cys, dCys, or dPen, and the peptide is cyclized through R2and R7via a disulfide bond. In further embodiments, R1is Nle, R5is Arg, R6is Trp and Y1and Y2are each independently dVal or dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[dCys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 296);Ac-Nle-c[dPen-Pro-dPhe-Arg-Trp-dPen]-dVal-dPro-NH2 (SEQ ID NO: 297);Ac-Nle-c[dCys-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 298);Ac-Nle-c[dCys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 299); andAc-Nle-c[dCys-Pro-p(F)dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 300), wherein c represents cyclization through R2and R7via a disulfide bond.

[0110] Alternatively, in some embodiments, R3is Pro and the sequence of any one of Formulae (l)-(IC) is cyclized through R2and R8. In further embodiments, R2is Asp, R7is Gly, and R8is Lys. In still further embodiments, R1is Nle, R4is dPhe, R5is Arg, and R6is Trp. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Gly-Lys]-dVal-dPro-NH2(SEQ ID NO: 301 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Gly-Lys]-dPro-dPro-Lys-Asp-NH2(SEQ ID NO: 302); andAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Gly-Lys]-dPro-dPro-dLys-dAsp-NH2(SEQ ID NO: 303), wherein c represents cyclization through R2and R8via a lactam bond.-78-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0111] In some embodiments, R3is Pro and R5is Arg. Alternatively, in some embodiments, R5is an amino acid other than Arg. In further embodiments, R5is Lys, His, transPro(guan), or cisPro(guan). In still further embodiments, R1is Nle, R2is Asp, R6is Trp, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Lys-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 304);Ac-Nle-c[Asp-Pro-dPhe-transPro(guan)-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 305);Ac-Nle-c[Asp-Pro-dPhe-cisPro(guan)-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 306);Ac-Nle-c[Asp-Pro-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 307); andAc-Nle-c[Asp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 308), wherein c represents cyclization through R2and R7via a lactam bond.

[0112] In some embodiments, R3is Pro and R6is Trp. Alternatively, in some embodiments, R6is an amino acid other than Trp. In further embodiments, R6is selected from dTrp, Phe, Nal(1 ’), Nal(2’), Aia, Aba, and Ata. In still further embodiments, R1is Nle, R2is Asp, R5is Arg, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 309);Ac-Nle-c[Asp-Pro-dPhe-Arg-Nal(1')-Lys]-dVal-dPro-NH2(SEQ ID NO: 310);Ac-Nle-c[Asp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2(SEQ ID NO: 311 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 312);Ac-Nle-c[Asp-Pro-dPhe-Arg-Aia-Lys]-dVal-dPro-NH2 (SEQ ID NO: 313);Ac-Nle-c[Asp-Pro-dPhe-Arg-Aba-Lys]-dVal-dPro-NH2 (SEQ ID NO: 314); andAc-Nle-c[Asp-Pro-dPhe-Arg-Ata-Lys]-dVal-dPro-NH2 (SEQ ID NO: 315), wherein c represents cyclization through R2and R7via a lactam bond.

[0113] In some embodiments, R3is Pro and Y1is dVal and Y2is dPro. Alternatively, in some embodiments, Y1is an amino acid other than dVal and Y2is an amino acid other than-79-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO dPro. In some embodiments, Y1is dVal and Y2is an amino acid other than dPro. In some embodiments, Y1is an amino acid other than dVal and Y2is dPro.

[0114] In some embodiments of the sequence of any one of Formulae (l)-(IC), Y1is dVal, Y2is dPro, and the C-terminus is modified by NH2. In some embodiments, Y1 is an amino acid other than dVal, Y2is an amino acid other than dPro, and the C-terminus is modified by NH2. In some embodiments, Y1is dVal, Y2is an amino acid other than dPro, and the C-terminus is modified by NH2. In some embodiments, Y1is an amino acid other than dVal, Y2is dPro, and the C-terminus is modified by NH2. In some embodiments, Y1is dVal, Y2is dPro, and the C-terminus is unmodified.

[0115] In embodiments of any one of Formulae (l)-(IC) when Y1is an amino acid other than dVal, then Y1is selected from dThr, dPro, Vai, p-Val, Hyp, dHyp, Pro, p-Pro, Ala, dAla, Gly, Asp, Arg, Asn, dAsp, dArg, dAsn, Lys, dLys, dLeu, and dTle. In embodiments of any one of Formulae (l)-(IC) when Y2is an amino acid other than dPro, then Y2is selected from dVal, Vai, p2Val, p3Val, Hyp, dHyp, Pro, pPro, Ala, dAla, Gly, Asp, dArg, dAsn, and dTle.

[0116] In some embodiments of the sequence of any one of Formulae (l)-(IC) when Y3is present and Y4-Y8are absent, then each of Y1, Y2, and Y3are independently selected from dThr, dArg, Arg, dLys, Lys, Vai, Pro, dVal, and dPro. In some embodiments of the sequence of any one of Formulae (l)-(IC) when Y3and Y4are present and Y5-Y8are absent, then each of Y1, Y2, Y3, and Y4are independently selected from dLys, Lys, Asp, dAsp, dVal, and dPro. In some embodiments of the sequence of any one of Formulae (l)-(IC) when Y3-Y5are present and Y6-Y8are absent, then each of Y1-Y5are independently selected from dVal and dPro. In some embodiments of the sequence of any one of Formulae (l)-(IC) when Y3-Y6are present and Y7-Y8are absent, then each of Y1-Y6are independently selected from dVal and dPro. In some embodiments of the sequence of any one of Formulae (l)-(IC) when Y3-Y7are present and Y8is absent, then each of Y1-Y7are independently selected from dVal and dPro. In some embodiments of the sequence of any one of Formulae (l)-(IC) when Y3-Y7are present, then each of Y1-Y7are independently selected from dVal and dPro.

[0117] Inclusion of one or more C-terminal residues, e.g., Y1-Y7, in the non-naturally occurring melanocortin analog of the present technology may enhance transport across the epithelium, the blood-brain barrier, and or the gastrointestinal tract. For example, peptides-80-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO comprising a C-terminus of dVal-dPro may have enhanced transport across the blood-brain barrier, relative to the same peptide without the dVal-dPro terminus. Accordingly, various C- terminal residue combinations provide enhanced deliverability and bioavailability of the present melanocortin analogs. In some embodiments, the C-terminus is dVal-dPro. Alternatively, in some embodiments, the C-terminus is not dVal-dPro. In further embodiments, R1is Nle, R2is Asp, R5is Arg, R6is Trp, R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Val-Pro-NH2 (SEQ ID NO: 316);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 317);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 318);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Val-NH2(SEQ ID NO: 319);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Pro-NH2(SEQ ID NO: 320);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dArg-NH2(SEQ ID NO: 321 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dPro-NH2(SEQ ID NO: 322);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 323);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 324);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Pro-Val-NH2(SEQ ID NO: 325);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-dVal-dPro-NH2(SEQ ID NO: 326);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2(SEQ ID NO: 327);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-Pro-Val-NH2(SEQ ID NO: 328);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-Val-Pro-NH2(SEQ ID NO: 329);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dVal-dPro-NH2(SEQ ID NO: 330);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 331 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dTle-dPro-NH2(SEQ ID NO: 332);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 333);-81 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dTle-NH2(SEQ ID NO: 334);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dPro-NH2(SEQ ID NO: 335);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 336);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 337);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dVal-dPro-NH2(SEQ ID NO: 338);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 339);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Trp-NH2(SEQ ID NO: 340);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-dPro-dVal-NH2(SEQ ID NO: 341 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-NH2(SEQ ID NO: 342);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dHyp-NH2(SEQ ID NO: 343);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dAsn-NH2(SEQ ID NO: 344);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-Asp-NH2(SEQ ID NO: 345);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asn-dPro-NH2(SEQ ID NO: 346);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Hyp-NH2(SEQ ID NO: 347);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Ala-Ala-NH2(SEQ ID NO: 348);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-NH2(SEQ ID NO: 349);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-dPro-NH2(SEQ ID NO: 350);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsn-dPro-NH2(SEQ ID NO: 351 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asn-NH2(SEQ ID NO: 352);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-NH2(SEQ ID NO: 353);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsn-NH2(SEQ ID NO: 354);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-dPro-NH2(SEQ ID NO: 355);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-OH (SEQ ID NO: 356);-82-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-OH (SEQ ID NO: 357);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2 (SEQ ID NO: 358);Ac-Nle-c[dAsp-Pro-dPhe-Arg-Trp-dLys]-dPro-dVal-NH2(SEQ ID NO: 359);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-pPro-p2Val-NH2 (SEQ ID NO: 360);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-pPro-p3Val-NH2 (SEQ ID NO: 361 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-pPro-pPro-NH2 (SEQ ID NO: 362);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2 (SEQ ID NO: 363);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2 (SEQ ID NO: 364);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 365);Ac-Nle-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 366); andAc-Nle-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 367), wherein c represents cyclization through R2and R7via a lactam bond.

[0118] In some embodiments of the sequence of any one of Formulae (l)-(IC), X1is present and is Nle and R1is present and is Nle. In some embodiments, X2is present and is Nle. In some embodiments, X3is present and is Nle. In some embodiments, when one or more of X1-X3is present, R1is Nle, R2is Asp, R5is Arg, R6is Trp, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 368);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 369); andAc-Nle-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 370), wherein c represents cyclization through R2and R7via a lactam bond.

[0119] In some embodiments of the sequence of any one of Formulae (l)-(IC), R3is His. In further embodiments, R4is dPhe, p(CI)dPhe, or p(F)dPhe.

[0120] In some embodiments, R3is His and the sequence of any one of Formulae (I)- (IC) is cyclized through R2and R7. In some embodiments, the sequence of any one of-83-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOFormulae (l)-(IC) is cyclized through R2and R7, and R2is Asp and R7is Lys. Alternatively, in some embodiments, R2is an amino acid capable of forming a linkage to the residue at R7other than Asp and / or R7is an amino acid capable of forming a linkage to the residue at R2other than Lys. For example, when R2is an amino acid other than Asp and / or R7is an amino acid other than Lys, the residue at R2may be capable of forming a linkage such as a lactam bond or a disulfide bond with the residue at R7.

[0121] In some embodiments, R2is Asp or Glu and R7is Orn, and the peptide is cyclized through R2and R7via a lactam bond. In further embodiments, R4is p(CI)dPhe. In still further embodiments, R1is Nle, R5is Arg, and R6is Trp. In some embodiments, the sequence of any one of Formulae (l)-(IC) is:Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 371 ); orAc-Nle-c[Glu-His-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 372), wherein c represents cyclization through R2and R7via a lactam bond.

[0122] In some embodiments, R2and R7are each independently Cys, dCys, or dPen, and the peptide is cyclized through R2and R7via a disulfide bond. In further embodiments, R1is Nle, R5is Arg, R6is Trp and Y1and Y2are each independently dVal or dPro. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[dCys-His-p(CI)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 373);Ac-Nle-c[dCys-His-p(CI)dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 374);Ac-Nle-c[Cys-His-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 375);Ac-Nle-c[dCys-His-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 376); andAc-Nle-c[dCys-His-p(F)dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 377), wherein c represents cyclization through R2and R7via a disulfide bond.

[0123] Alternatively, in some embodiments, R3is His and the sequence of any one of Formulae (l)-(IC) is cyclized through R2and R8. In further embodiments, R2is Asp, R7is Pro, and R8is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is: Ac--84-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WONle-c[Asp-His-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 378), wherein c represents cyclization through R2and R8via a lactam bond.

[0124] In some embodiments, R3is His, R5is Arg and R6is Trp. Alternatively, in some embodiments, R5is an amino acid other than Arg and / or R6is an amino acid other than Trp. In some embodiments, R5is transPro(guan) or cisPro(guan). In further embodiments, R6is dNal(2’) or Nal(2’). In still further embodiments, R1is Nle, R2is Asp, and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-His-dPhe-transPro(guan)-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 379);Ac-Nle-c[Asp-His-dPhe-cisPro(guan)-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 380);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 381 ); andAc-Nle-c[Asp-His-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 390), wherein c represents cyclization through R2and R7via a lactam bond.

[0125] In some embodiments, R3is His and Y1is dVal and Y2is dPro. Alternatively, in some embodiments, Y1is an amino acid other than dVal and Y2is an amino acid other than dPro. In some embodiments, Y1is dVal and Y2is an amino acid other than dPro. In some embodiments, Y1is an amino acid other than dVal and Y2is dPro. In further embodiments, R4is p(CI)dPhe. In still further embodiments, R2is Asp, R5is Arg, R6is Trp and R7is Lys. In some embodiments, the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 382)Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 383);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 384);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 385); andAc-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 386), wherein c represents cyclization through R2and R7via a lactam bond.-85-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0126] In some embodiments, the non-naturally occurring melanocortin analog comprises a sequence of any one of SEQ ID NOs: 2, 4, 169-386, and 390.

[0127] In some embodiments, the non-naturally occurring melanocortin analog is in the form of a salt. In further embodiments, the non-naturally occurring melanocortin analog is in the form of an acetate salt. In still further embodiments, the non-naturally occurring melanocortin analog is in the form of an acetate salt and comprises a sequence of any one of Formulae (l)-(IC). In yet further embodiments, the non-naturally occurring melanocortin analog is in the form of an acetate salt and comprises a sequence of any one of the sequences provided above.

[0128] The non-naturally occurring melanocortin analog may be present in the pharmaceutical composition in an amount sufficient to elicit the desired therapeutic activity. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition in an amount sufficient to treat, prevent, or reduce symptoms associated with the disease or condition. In further embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition in an amount sufficient to induce a desirable outcome in the subject having the disease or condition.

[0129] The pharmaceutical composition may include a non-naturally occurring melanocortin analog at a concentration of about 0.01 mg / mL to about 200 mg / mL. For example, in some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 175 mg / mL, about 0.02 mg / mL to about 150 mg / mL, about 0.04 mg / mL to about 100 mg / mL, about 0.05 mg / mL to about 50 mg / mL, about 0.06 mg / mL to about 20 mg / mL, about 0.08 mg / mL to about 15 mg / mL, or about 0.1 mg / mL to about 10 mg / mL. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 9 mg / mL, about 0.01 mg / mL to about 8 mg / mL, about 0.01 mg / mL to about 7 mg / mL, about 0.01 mg / mL to about 6 mg / mL, about 0.01 mg / mL to about 5 mg / mL, about 0.01 mg / mL to about 4 mg / mL, about 0.01 mg / mL to about 3 mg / mL, about 0.01 mg / mL to about 2 mg / mL, about 0.05 mg / mL to about 2 mg / mL, about 0.05 mg / mL to about 5 mg / mL, about 0.1 mg / mL to about 50 mg / mL, about 0.1 mg / mL to about 25 mg / mL, about 0.1 mg / mL to about 10 mg / mL, about 0.1 mg / mL-86-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO to about 5 mg / mL, about 0.1 mg / mL to about 2.5 mg / mL, about 0.1 mg / mL to about 1.5 mg / mL, about 0.5 mg / mL to about 1 .5 mg / mL, or about 1 mg / mL. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition at a concentration of about 10 mg / mL to about 200 mg / mL, about 20 mg / mL to about 200 mg / mL, about 60 mg / mL to about 200 mg / mL, about 80 mg / mL to about 200 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 180 mg / mL, about 120 mg / mL to about 180 mg / mL, about 120 mg / mL to about 160 mg / mL, about 10 mg / mL to about 100 mg / mL, about 20 mg / mL to about 80 mg / mL, or about 20 mg / mL to about 60 mg / mL.

[0130] The pharmaceutical compositions of the present technology may be formulated to deliver a certain dose of the non-naturally occurring melanocortin analog to a subject in need thereof. The dose may be based on the body weight of the subject. For example, in some embodiments, the pharmaceutical composition is formulated to deliver the non- naturally occurring melanocortin analog to the subject at a dose of about 0.01 mg / kg to about 1000 mg / kg, per body weight of the subject. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the non-naturally occurring melanocortin analog of about 0.01 mg / kg to about 50 mg / kg, about 0.01 mg / kg to about 40 mg / kg, about 0.05 mg / kg to about 30 mg / kg, about 0.1 mg / kg to about 20 mg / kg, about 0.25 mg / kg to about 10 mg / kg, about 0.5 mg / kg to about 7.5 mg / kg, about 0.75 mg / kg to about 7 mg / kg, about 1 mg / kg to about 6.5 mg / kg, or about 1 mg / kg to about 6 mg / kg, per body weight of the subject. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the non-naturally occurring melanocortin analog of about 0.01 mg / kg to about 10 mg / kg, about 0.01 mg / kg to about 7.5 mg / kg, about 0.01 mg / kg to about 5 mg / kg, about 0.01 mg / kg to about 2.5 mg / kg, about 0.01 mg / kg to about 1.5 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 7.5 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 2.5 mg / kg, or about 0.1 mg / kg to about 1.5 mg / kg, per body weight of the subject. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of melanocortin analog of about 0.1 mg / kg, about 0.25 mg / kg, about 0.5 mg / kg, about 0.75 mg / kg, 1 mg / kg, about 2.5 mg / kg, about 5 mg / kg, about 7.5 mg / kg, about 10 mg / kg, about 12.5 mg / kg, about 15 mg / kg, about 17.5 mg / kg, about 20 mg / kg, about 22.5 mg / kg, or about 25 mg / kg, per body weight of the subject. In further embodiments, the-87-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO pharmaceutical composition is formulated to deliver a dose of the non-naturally occurring melanocortin analog of about 5 mg / kg, per body weight of the subject.

[0131] In some embodiments, the pharmaceutical composition includes the non- naturally occurring melanocortin analog in an amount sufficient to deliver about 0.01 mg / kg to about 1000 mg / kg of the non-naturally occurring melanocortin analog to the subject in need thereof. For example, in some embodiments, the pharmaceutical composition is formulated to deliver the non-naturally occurring melanocortin analog to the subject at a dose of about 1 .0 mg to about 20 g. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition in an amount of about 5 mg to about 15 g, about 10 mg to about 10 g, about 100 mg to about 5 g, about 250 mg to about 2.5 g, about 250 mg to about 1 g, about 500 mg to about 5 g, about 500 mg to about 2.5 g, about 500 mg to about 1 g, or about 250 mg to about 750 mg.

[0132] In some embodiments, the pharmaceutical composition includes the non- naturally occurring melanocortin analog in an amount sufficient to deliver about 0.01 mg / kg to about 10 mg / kg of the non-naturally occurring melanocortin analog to the subject in need thereof. For example, in some embodiments, the pharmaceutical composition is formulated to deliver the non-naturally occurring melanocortin analog to the subject at a dose of about 1 .0 mg to about 5000 mg. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition in an amount of about 2.5 mg to about 2500 mg, about 5 mg to about 2000 mg, about 10 mg to about 1500 mg, or about 20 mg to about 1000 mg. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition in an amount of about 0.5 mg to about 500 mg, about 1 mg to about 250 mg, about 2.5 mg to about 100 mg, about 5 mg to about 75 mg, about 10 mg to about 60 mg, or about 20 mg to about 50 mg. In some embodiments, the non-naturally occurring melanocortin analog is present in the pharmaceutical composition in an amount of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg,-88-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1 100 mg, about 1200 mg, about 1300 mg, about 1400 mg, or about 1500 mg.

[0133] In some embodiments, the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers and / or excipients. In some embodiments, the excipient comprises or consists of an enzyme inhibitor, such as a protease inhibitor. The excipient may comprise one or more compounds which inhibit, bind, or otherwise target an enzyme selected from a phosphatase (e.g., an intestinal phosphatase), a protease (e.g., a metalloprotease, an endopeptidase, or an amino peptidase). The protease may be a trypsin, a trypsin-like protease, a chymotrypsin, an elastase, a pepsin, a mesotrypsin, a tryptase, and a chymase. In some embodiments, the excipient may comprise one or more compounds which inhibit, bind, or otherwise target an enzyme of the digestive tract, such as an intestinal enzyme.

[0134] Nonlimiting examples of suitable enzyme inhibitors used in accordance with the embodiments of the present technology include sodium fluoride, ethylenediaminetetraacetic acid (EDTA), aprotinin, pepstatin, bestatin, bacitracin, boric acid, a soybean trypsin inhibitor (SBTI), a Bowman-Birk inhibitor (BBI), and a Kunitz trypsin inhibitor (KTI).

[0135] In other embodiments, the pharmaceutical composition does not comprise any pharmaceutically acceptable carriers or excipients. Pharmaceutically acceptable carriers and / or excipients included in the pharmaceutical compositions of the present technology may be selected based on the carrier or excipient’s ability to confer desirable properties, such as reduced or lack of delivery site reactions, solubility, stability, pH, buffering, pharmacokinetics, bioavailability, and the like, to the pharmaceutical composition. For example, the one or more pharmaceutically acceptable carriers and / or excipients may be included in the pharmaceutical compositions described herein to provide improved pharmacokinetic properties and oral bioavailability.

[0136] The pharmaceutical compositions of the present technology may include at least one permeation enhancer. Inclusion of at least one permeation enhancer in the compositions and formulations of the present technology improves the pharmacokinetic properties and oral bioavailability of the non-naturally occurring melanocortin analog such as, for example, uptake and stability of the non-naturally occurring melanocortin analog in-89-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO plasma and cerebrospinal fluid (CSF), as compared to a pharmaceutical composition or a formulation thereof of the non-naturally occurring melanocortin analog without the permeation enhancer. In some embodiments, the permeation enhancer is included in the pharmaceutical composition in an amount sufficient to achieve at least about a 2-fold increase, at least about a 3-fold increase, at least about a 4-fold increase, or at least about a 5-fold increase in a maximum concentration (Cmax) and / or area under the curve (AUG) values in a subject, relative to a pharmaceutical composition of the non-naturally occurring melanocortin analog without the permeation enhancer. For example, the permeation enhancer may be present in the pharmaceutical composition in an amount sufficient to achieve Cmax and / or AUG levels at least about 5 times, at least about 10 times, at least about 15 times, or at least about 20 times greater that Cmax and AUG levels achieved with a pharmaceutical composition of the non-naturally occurring melanocortin analog without the permeation enhancer.

[0137] The permeation enhancers may be GRAS when the pharmaceutical compositions or formulations thereof are used under one or more conditions of the present technology. In some embodiments, the permeation enhancer is a GRAS permeation enhancer. As will be appreciated, GRAS substances receive a Type of Conclusion score from the Select Committee on GRAS Substances (SCOGS), which further classifies substances based on how hazardous the substance is to the public at current consumption rates and use conditions and how hazardous the substance may be at increased consumption rates and different use conditions according to the available evidence, with a score of 1 representing the least potentially hazardous substances and a score of 5 representing the most potentially hazardous substances based on the current evidence. In some embodiments, the GRAS permeation enhancer has a SCOGS Type of Conclusion of Conclusion score of 1 or 2. In further embodiments, the GRAS permeation enhancer has a SCOGS Type of Conclusion score of 1 .

[0138] In some embodiments, the permeation enhancer is an inactive ingredient when used under one or more conditions of the present technology. For example, the permeation enhancer may be included in the U.S. Food and Drug Administration (FDA) Inactive Ingredient Database (IID) for route of administration (ROA) and quantity, or it may be-90-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO qualified into the IID as a novel excipient. Likewise, the permeation enhancer may be considered inactive and / or otherwise safe by the European Medicines Agency (EMA), Health Canada, the International Pharmaceutical Excipient Council (IPEC), and / or other national health and drug agencies.

[0139] The permeation enhancers of the present technology and their respective amounts may be selected based on a desired modification in a pharmacokinetic (PK) or pharmacodynamic (PD) metric, relative to a control (e.g., a pharmaceutical composition or formulation lacking the permeation enhancers or having a different amount of the permeation enhancers). For example, the permeation enhancers and / or their respective amounts may be selected to increase an area under the curve (AUG) value of a pharmaceutical composition or formulation, relative to a control. The increase in the AUG value may comprise an increase in at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control. In another example, the permeation enhancers and / or their respective amounts may be selected to increase a maximum concentration (Cmax) value of a pharmaceutical composition or formulation, relative to a control. The increase in the Cmax value may comprise an increase in at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0140] In some embodiments, the pharmaceutical compositions of the present technology comprise one or more permeation enhancers. In some embodiments, the pharmaceutical compositions of the present technology comprise two or more permeation enhancers. In some embodiments, the permeation enhancer is selected from caprylic acid, salcaprozate sodium (SNAG), sodium caprate, sodium chenodeoxycholate, and propyl gallate. In some embodiments, the permeation enhancer is propyl gallate. In some embodiments, the permeation enhancer is a GRAS permeation enhancer. The GRAS permeation enhancer may comprise a substance included on the U.S. Food & Drug Administration’s GRAS Substances SCOGS Database.

[0141] The permeation enhancer may be present in the pharmaceutical composition in at a concentration of about 0.01 mg / mL to about 100 mg / mL. For example, in some-91 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO embodiments, the permeation enhancer is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 75 mg / mL, about 0.025 mg / mL to about 50 mg / mL, about 0.05 mg / mL to about 40 mg / mL, about 0.075 mg / mL to about 30 mg / mL, or about 0.1 mg / mL to about 25 mg / mL. In some embodiments, the permeation enhancer is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 10 mg / mL, about 0.1 mg / mL to about 7.5 mg / mL, about 0.1 mg / mL to about 5 mg / mL, about 0.1 mg / mL to about 2.5 mg / mL, about 0.1 mg / mL to about 2 mg / mL, about 0.1 mg / mL to about 1.5 mg / mL, or about 0.1 mg / mL to about 1 mg / mL. In some embodiments, the permeation enhancer is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 25 mg / mL, about 0.2 mg / mL to about 20 mg / mL, about 0.3 mg / mL to about 15 mg / mL, about 0.4 mg / mL to about 12 mg / mL, about 0.5 mg / mL to about 10 mg / mL, or about 1 mg / mL to about 5 mg / mL. In some embodiments, the permeation enhancer is present in the pharmaceutical composition at a concentration of about 1 mg / mL to about 20 mg / mL, about 2 mg / mL to about 15 mg / mL, about 3 mg / mL to about 10 mg / mL, or about 4 mg / mL to about 8 mg / mL. In some embodiments, the permeation enhancer is present in the pharmaceutical composition at a concentration of about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, or about 10 mg / mL. In further embodiments, the permeation enhancer is present in the pharmaceutical composition at a concentration of about 6 mg / mL.

[0142] The pharmaceutical compositions of the present technology may be formulated to deliver a certain dose of the permeation enhancer to a subject. The dose may be based on the body weight of the subject. For example, in some embodiments, the pharmaceutical composition is formulated to deliver the permeation enhancer to the subject at a dose of about 0.1 mg / kg to about 200 mg / kg per body weight of the subject. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the permeation enhancer of about 0.1 mg / kg to about 175 mg / kg, about 0.25 mg / kg to about 150 mg / kg, about 0.5 mg / kg to about 125 mg / kg, about 0.5 mg / kg to about 100 mg / kg, about 0.75 mg / kg to about 75 mg / kg, about 1 .0 mg / kg to about 60 mg / kg, about 1 .5 mg / kg to about 50 mg / kg, or about 2.0 mg / kg to about 40 mg / kg. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the permeation enhancer of about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 7.5 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1-92-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO mg / kg to about 2.5 mg / kg, about 0.1 mg / kg to about 2 mg / kg, about 0.1 mg / kg to about 1 .5 mg / kg, or about 0.1 mg / kg to about 1 mg / kg. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the permeation enhancer of about 1 mg / kg to about 200 mg / kg, about 1 mg / kg to about 150 mg / kg, about 1 mg / kg to about 100 mg / kg, about 1 mg / kg to about 50 mg / kg, about 1 mg / kg to about 25 mg / kg, about 1 mg / kg to about 20 mg / kg, about 1 mg / kg to about 15 mg / kg, about 1 mg / kg to about 12 mg / kg, about 1 mg / kg to about 10 mg / kg, or about 1 mg / kg to about 5 mg / kg. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the permeation enhancer of about 1 mg / kg, about 5 mg / kg, about 10 mg / kg, about 15 mg / kg, 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 55 mg / kg, about 60 mg / kg, about 70 mg / kg, about 80 mg / kg, about 90 mg / kg, about 100 mg / kg about 125 mg / kg, about 150 mg / kg, about 175 mg / kg, or about 200 mg / kg. In further embodiments, the pharmaceutical composition is formulated to deliver a dose of the permeation enhancer of about 30 mg / kg.

[0143] In some embodiments, the pharmaceutical composition includes the permeation enhancer in an amount sufficient to deliver about 1.0 mg / kg to about 40 mg / kg of the permeation enhancer to the subject in need thereof. In some embodiments, the permeation enhancer is present in the pharmaceutical composition in an amount of about 10 mg to about 3000 mg. In some embodiments, the permeation enhancer is present in the pharmaceutical composition in an amount of about 25 mg to about 2500 mg, about 50 mg to about 2000 mg, about 100 mg to about 1500 mg, or about 150 mg to about 1000 mg. In some embodiments, the permeation enhancer is present in the pharmaceutical composition in an amount of about 10 mg to about 900 mg, about 15 mg to about 800 mg, about 20 mg to about 700 mg, about 25 mg to about 600 mg, about 30 mg to about 500 mg, about 35 mg to about 400 mg, about 40 mg to about 300 mg, about 45 to about 200 mg, or about 50 mg to about 100 mg. In some embodiments, the permeation enhancer is present in the pharmaceutical composition in an amount of about 100 mg to about 3000 mg, about 150 mg to about 2500 mg, about 200 mg to about 2250 mg, about 250 mg to about 2000 mg, about 300 mg to about 1750 mg, about 350 mg to about 1500 mg, about 400 mg to about 1250 mg, or about 500 mg to about 1000 mg. In some embodiments, the permeation enhancer is present in the pharmaceutical composition in an amount of about 10 mg, about 20 mg, about 30 mg, about-93-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, or about 900 mg. In some embodiments, the permeation enhancer is present in the pharmaceutical composition in an amount of about 1000 mg, about 1200 mg, about 1500 mg, about 1700 mg, about 2000 mg, about 2200 mg, about 2500 mg, about 2700 mg, or about 3000 mg.

[0144] In some embodiments, the permeation enhancer is propyl gallate and the propyl gallate is present in the pharmaceutical composition or at a concentration of about 0.1 mg / mL to about 100 mg / mL. In some embodiments, the propyl gallate is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 75 mg / mL, about 0.025 mg / mL to about 50 mg / mL, about 0.05 mg / mL to about 40 mg / mL, about 0.075 mg / mL to about 30 mg / mL, or about 0.1 mg / mL to about 25 mg / mL. In some embodiments, the propyl gallate is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 10 mg / mL, about 0.1 mg / mL to about 7.5 mg / mL, about 0.1 mg / mL to about 5 mg / mL, about 0.1 mg / mL to about 2.5 mg / mL, about 0.1 mg / mL to about 2 mg / mL, about 0.1 mg / mL to about 1.5 mg / mL, or about 0.1 mg / mL to about 1 mg / mL. In some embodiments, the propyl gallate is present in the pharmaceutical composition at a concentration of about 0.01 mg / mL to about 25 mg / mL, about 0.2 mg / mL to about 20 mg / mL, about 0.3 mg / mL to about 15 mg / mL, about 0.4 mg / mL to about 12 mg / mL, about 0.5 mg / mL to about 10 mg / mL, or about 1 mg / mL to about 5 mg / mL. In some embodiments, the propyl gallate is present in the pharmaceutical composition at a concentration of about 1 mg / mL to about 20 mg / mL, about 2 mg / mL to about 15 mg / mL, about 3 mg / mL to about 10 mg / mL, or about 4 mg / mL to about 8 mg / mL. In some embodiments, the propyl gallate is present in the pharmaceutical composition at a concentration of about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, or about 10 mg / mL. In further embodiments, propyl gallate is present in the pharmaceutical composition at a concentration of about 6 mg / mL.

[0145] In some embodiments, the pharmaceutical composition is formulated to deliver the propyl gallate to the subject at a dose of about 0.1 mg / kg to about 200 mg / kg per body weight of the subject. In some embodiments, the pharmaceutical composition is formulated-94-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO to deliver a dose of the propyl gallate of about 0.1 mg / kg to about 175 mg / kg, about 0.25 mg / kg to about 150 mg / kg, about 0.5 mg / kg to about 125 mg / kg, about 0.5 mg / kg to about 100 mg / kg, about 0.75 mg / kg to about 75 mg / kg, about 1 .0 mg / kg to about 60 mg / kg, about 1 .5 mg / kg to about 50 mg / kg, or about 2.0 mg / kg to about 40 mg / kg. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of propyl gallate of about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 7.5 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 2.5 mg / kg, about 0.1 mg / kg to about 2 mg / kg, about 0.1 mg / kg to about 1 .5 mg / kg, or about 0.1 mg / kg to about 1 mg / kg. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of propyl gallate of about 1 mg / kg to about 200 mg / kg, about 1 mg / kg to about 150 mg / kg, about 1 mg / kg to about 100 mg / kg, about 1 mg / kg to about 50 mg / kg, about 1 mg / kg to about 25 mg / kg, about 1 mg / kg to about 20 mg / kg, about 1 mg / kg to about 15 mg / kg, about 1 mg / kg to about 12 mg / kg, about 1 mg / kg to about 10 mg / kg, or about 1 mg / kg to about 5 mg / kg. In some embodiments, the pharmaceutical composition is formulated to deliver a dose of the propyl gallate of about 1 mg / kg, about 5 mg / kg, about 10 mg / kg, about 15 mg / kg, 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 55 mg / kg, about 60 mg / kg, about 70 mg / kg, about 80 mg / kg, about 90 mg / kg, about 100 mg / kg, about 125 mg / kg, about 150 mg / kg, about 175 mg / kg, or about 200 mg / kg. In further embodiments, the pharmaceutical composition is formulated to deliver a dose of the propyl gallate of about 30 mg / kg.

[0146] In some embodiments, the pharmaceutical composition includes the propyl gallate in an amount sufficient to deliver about 1 .0 mg / kg to about 40 mg / kg of the propyl gallate to the subject in need thereof. In some embodiments, the propyl gallate is present in the pharmaceutical composition in an amount of about 10 mg to about 3000 mg. In some embodiments, propyl gallate is present in the pharmaceutical composition in an amount of about 25 mg to about 2500 mg, about 50 mg to about 2000 mg, about 100 mg to about 1500 mg, or about 150 mg to about 1000 mg. In some embodiments, the propyl gallate is present in the pharmaceutical composition in an amount of about 10 mg to about 900 mg, about 15 mg to about 800 mg, about 20 mg to about 700 mg, about 25 mg to about 600 mg, about 30 mg to about 500 mg, about 35 mg to about 400 mg, about 40 mg to about 300 mg, about 45 to about 200 mg, or about 50 mg to about 100 mg. In some embodiments, the propyl gallate-95-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO is present in the pharmaceutical composition in an amount of about 100 mg to about 3000 mg, about 150 mg to about 2500 mg, about 200 mg to about 2250 mg, about 250 mg to about 2000 mg, about 300 mg to about 1750 mg, about 350 mg to about 1500 mg, about 400 mg to about 1250 mg, or about 500 mg to about 1000 mg. In some embodiments, the propyl gallate is present in the pharmaceutical composition in an amount of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, or about 900 mg. In some embodiments, the propyl gallate is present in the pharmaceutical composition in an amount of about 1000 mg, about 1200 mg, about 1500 mg, about 1700 mg, about 2000 mg, about 2200 mg, about 2500 mg, about 2700 mg, or about 3000 mg.

[0147] The pharmaceutical compositions of the present technology further comprise water. The water may be water for injection (WFI), sterile water, bacteriostatic water for injection (BWFI), distilled water, bidistilled water, deionized water, deionized distilled water, and reverse osmosis water. In some embodiments, the water present in the pharmaceutical composition is water for injection. In some embodiments, the water present in the pharmaceutical composition is water further comprises a salt, such as, for example, sodium chloride. In some embodiments, the pharmaceutical composition comprises saline.Dosage Units

[0148] The present technology also provides oral dosage units of the pharmaceutical compositions described herein. In some embodiments, the oral dosage units are in the form of any dosage unit suitable for oral administration, such as, for example, a pill, a capsule, a powder, a granule, and a film. The oral dosage units may include any form of delivery of the pharmaceutical compositions to a subject where the pharmaceutical compositions are placed in the mouth of the subject, whether or not the pharmaceutical compositions are swallowed. The oral administration may include buccal and sublingual as well as esophageal administration.

[0149] In some embodiments, the oral dosage unit is a solid oral dosage unit. For example, a solid dosage unit may be in the form of a pill, a capsule, or a powder. In some-96-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO embodiments, the oral pharmaceutical composition is in the form of a pill. Non-limiting examples of pill formulations include tablets, pellets, caplets, and lozenges. In some embodiments, the pill is in the form of a tablet. The tablet may be prepared in various forms such as, for example, an orally disintegrating tablet, a mucoadhesive tablet, enteric coated tablet, gastroresistant tablet, powder-filled capsule, caplet, dispersible tablet, a sublingual tablet, a buccal tablet, a chewable tablet, an effervescent tablet, and a lozenge tablet.

[0150] The solid oral dosage unit may be formulated with one or more excipients to improve administration and deliverability of the pharmaceutical composition. For example, the solid oral dosage unit may include one or more diluents, binders, disintegrants, lubricants, glidants, and coatings. In some embodiments, the solid oral dosage unit is formulated with a coating, such as, for example, and enteric coating.

[0151] In one embodiment, the composition is present in a capsule. In some embodiments, the capsule comprises one or more of a gelatin (e.g., a soft gelatin capsule), hydroxypropyl methylcellulose, pullulan, a sugar or starch derivative (e.g., cellulose derivatives, gelatin, vegetable oils, and polyethylene glycols), carrageenan, a plasticizer (e.g., glycerin or sorbitol), a colorant, a preservative (e.g., potassium sorbate, phenol, benzyl alcohol, meta-cresol, methyl paraben, propyl paraben, octadecyldimethylbenzyl ammonium chloride, benzalkonium halides, hexamethonium chloride, alkyl parabens such as methyl or propyl paraben, catechol, resorcinol, cyclohexanol, and 3-pentanol), an antioxidant (e.g., ascorbic acid, methionine, and vitamin E), or an opacifier (e.g., titanium dioxide). The capsule may be a liquid-filled capsule or a semi-solid-filled capsule, or a solid-filled capsule.

[0152] In some embodiments, the capsule is filled with an aqueous suspension comprising the non-naturally occurring melanocortin analog. In some embodiments, the non-naturally occurring melanocortin analog is suspended in water. In other embodiments, the non-naturally occurring melanocortin analog is suspended in saline.

[0153] The dosage unit may comprise a non-naturally occurring melanocortin analog in any purified form. For example, the non-naturally occurring melanocortin analog present in the dosage unit may be lyophilized, crystallized, spray-dried, or precipitated. In some embodiments, the dosage unit comprises lyophilized non-naturally occurring melanocortin analog. In some embodiments, the dosage unit comprises spray-dried non-naturally-97-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO occurring melanocortin analog. In some embodiments, the dosage unit comprises crystalized non-naturally occurring melanocortin analog. In some embodiments, the dosage unit comprises precipitated non-naturally occurring melanocortin analog.Methods of Administration

[0154] The pharmaceutical compositions comprising the non-naturally occurring melanocortin analog of the present technology may be administered to a subject via oral administration. In some embodiments, the pharmaceutical composition is orally administered to the subject via an oral dosage unit. In some embodiments, the pharmaceutical composition is orally administered to the subject via a tablet or a capsule. In some embodiments, the pharmaceutical composition is orally administered to the subject via a tablet.

[0155] In some embodiments, the pharmaceutical composition comprising the non- naturally occurring melanocortin analog is administered hourly (such as every hour, every 2 hours, every 4 hours, every 8 hours, etc.), once a day, or twice a day. In some embodiments, the non-naturally occurring melanocortin analog is administered every morning, every evening, or every afternoon. In some embodiments, the pharmaceutical composition is orally administered before a meal, after a meal, or with a meal.

[0156] In some embodiments, the pharmaceutical composition comprising the non- naturally occurring melanocortin analog is administered as a dosing regimen comprising once, twice, or three times daily oral administration on a (i) weekly; (ii) every other week; (iii) one week of therapy followed by two, three or four weeks off; (iv) two weeks of therapy followed by one, two, three or four weeks off; (v) three weeks of therapy followed by one, two, three, four or five week off; (vi) four weeks of therapy followed by one, two, three, four or five week off; (vii) five weeks of therapy followed by one, two, three, four or five week off; or (viii) monthly schedule. The (i)-(viii) schedules may be repeated 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , or 12 times or more. In some embodiments, the pharmaceutical composition is administered so as to deliver various dosages of the non-naturally occurring melanocortin analog during the dosing regimen (e.g., a first dose with an effective amount of 10 mg / kg of the melanocortin analog and a second dose with an effective amount of 5 mg / kg of the melanocortin analog).-98-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0157] In some embodiments, the pharmaceutical composition is administered once every other day, once every 2 or 3 days, once every third day, once per week, once every other week, once every third week, once every month, once every six weeks, once every other month, once every three months, once every six months, or once per year. Administration of the pharmaceutical composition comprising the non-naturally occurring melanocortin analog at any of the dosing frequencies of the present technology may be repeated for a total of at least 2 dosages, at least 3 dosages, at least 4 dosages, at least 5 dosages, at least 10 dosages, at least 15 dosages, at least 20 dosages, at least 30 dosages, at least 40 dosages, at least 50 dosages or more. In some embodiments, the frequency of dosages of the pharmaceutical composition is the same during a treatment regimen. In other embodiments, the frequency of dosages of pharmaceutical composition is different during a treatment regimen. The pharmaceutical composition may be administered even less frequently. Alternatively, the dosage regimen may be decreased or increased from an initial dosing regimen for days, weeks, months, or years. In some embodiments, the dosing regimen is repeated at other intervals.

[0158] In some embodiments, the pharmaceutical composition is administered at least once daily to deliver a dose of the non-naturally occurring melanocortin analog of about 0.001 mg / kg to 25 mg / kg, 0.01 mg / kg to 20 mg / kg, 0.05 mg / kg to 15 mg / kg, 0.075 mg / kg to 10 mg / kg, 0.1 mg / kg to 8 mg / kg, 0.2 mg / kg to 6 mg / kg, 0.3 mg / kg to 4 mg / kg, 0.4 mg / kg to 2 mg / kg, or 0.5 mg / kg to 1 mg / kg per body weight of the subject. In some embodiments, the pharmaceutical composition is administered at least once daily to deliver a dose of the non-naturally occurring melanocortin analog of about 0.5 mg / kg to about 10 mg / kg, about 1 mg / kg to about 7.5 mg / kg, or about 2.5 mg / kg to about 5 mg / kg per body weight of the subject.

[0159] The administration methods described herein may be performed on the subject for at least 1 day, 1 week, 1 month, 3 months, 6 months, 1 year, or 5 years. In some embodiments, the pharmaceutical composition is administered to the subject for at least 1 day, at least 2 days, at least 5 days, at least 6 days, at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at-99-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO least 9 months, at least 1 year, at least 2 years, at least 3 years, at least 4 years, or at least 5 years.

[0160] In some embodiments, an administration method described herein is performed on the subject for 1 day, 7 days, 14 days, 21 days, 28 days, 35 days, 40 days, 45 days, 50 days, 60 days, 75 days, 90 days, 100 days, 110 days, or 120 days.

[0161] In some embodiments, the pharmaceutical composition is administered to a subject in a continuous doing schedule. As used herein, a “continuous dosing schedule” is an administration or dosing regimen without dose interruptions, e.g., without days off treatment. Repetition of 21 -day or 28-day treatment cycles without dose interruptions is an exemplary continuous dosing schedule.

[0162] In some embodiments, administration of pharmaceutical composition comprising the non-naturally occurring melanocortin analog comprises delivery of the melanocortin analog across the blood brain barrier. In some embodiments, administration of the pharmaceutical composition comprises delivery of the melanocortin analog across the epithelium. In some embodiments, administration of the pharmaceutical composition comprises delivery of the melanocortin analog across the epithelium and the blood brain barrier. In some embodiments, administration of the pharmaceutical composition comprises delivery of the melanocortin analog through the gastrointestinal tract.

[0163] In some embodiments, the non-naturally occurring melanocortin analogs comprise one or more of the following features (i) blood brain barrier passage, (ii) one or more pharmaceutical-like pharmacokinetic measurements (e.g., a pharmacokinetic measurement of an opioid agonist agent pharmaceutical or an oral melanocortin agonist pharmaceutical), (iii) degradation resistance; (iv) equipotency (e.g., partial or full agonism) on MC3R and MC4R activity, and (v) are orally available (e.g, oral potency). In some embodiments, the oral potency is greater than a subcutaneous administration potency for an equivalent dose. In some embodiments, the non-naturally occurring melanocortin analogs comprise two or more of (i)-(v). In some embodiments, the non-naturally occurring melanocortin agonists comprise each of (i)-(v).-100-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOPharmacokinetics and Pharmacodynamics

[0164] The non-naturally occurring melanocortin analogs in the pharmaceutical compositions of the present technology exhibit pharmacokinetic (pK) and / or pharmacodynamic (pD) parameters. Such pK and / or pD may be expressed or otherwise determined relative to a control, which, in some instances, may be a non-naturally occurring melanocortin analog in a pharmaceutical composition lacking one or more features of the pharmaceutical compositions of the present technology. For example, the control may be a non-naturally occurring melanocortin analog in a pharmaceutical composition lacking one or more permeation enhancers of the present technology.

[0165] In some embodiments, the pK and / or pD of the non-naturally occurring melanocortin analogs may be assessed using concentration and / or temporal measurements (e.g., Tfinai, Cmax, T1 / 2 (h)), AUG, or T max. In some embodiments, the non-naturally occurring melanocortin analogs have reduced clearance and / or metabolism, increased uptake, absorption, and / or stability, relative to a control.Clearance

[0166] “Clearance” may refer to the elimination, absorption, and / or metabolism of the non-naturally occurring melanocortin analogs in the subject’s plasma. Clearance may be assessed as volume of plasma cleared of the non-naturally occurring melanocortin analogs over time (e.g., mL / min, L / hr, or L / day) and / or may be normalized to body weight of the subject (e.g., mL / min / kg). Reduced clearance may also be represented by an increase in half-life or volume of distribution (Vd). In some embodiments, measuring clearance comprises measuring a terminal elimination rate constant (Az) or an inter-compartmental clearance (Q).

[0167] In some embodiments, the reduction in clearance comprises a measurement about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after oral administration of the non-naturally occurring melanocortin analog.

[0168] In some embodiments, the reduction in clearance comprises a measurement during oral administration of the non-naturally occurring melanocortin analog. In some-101 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO embodiments, the reduction in clearance comprises a measurement at the completion of oral administration of the non-naturally occurring melanocortin analog.Concentration

[0169] In some embodiments, oral administration of the pharmaceutical compositions of the present technology result in an increased tissue, plasma, and / or serum concentration of the non-naturally occurring melanocortin analog relative to a control. “Concentration” may comprise a measurement reflecting one or more of the absolute amounts of the non-naturally occurring melanocortin analog, the absorption of the non-naturally occurring melanocortin analog, the metabolism of non-naturally occurring melanocortin analog, or the elimination of non-naturally occurring melanocortin analog.

[0170] The increased tissue, plasma, and / or serum concentration may be an increase in concentration of the non-naturally occurring melanocortin analog at a given time point relative to a control administered at the same dose and measured at the same time point. The concentration may be measured at an intermediate time point or a final time point and may be measured as a mean residence time (MRT), an average concentration (Cavg), a trough concentration (Ctrough), or a concentration at the end of administration (e.g., infusion) time (CT).

[0171] In some embodiments, the increased concentration is reflected by an increase in peak plasma concentration (Cmax). An increase in Cmax may suggest increased absorption, reduced metabolism, or slower elimination of the non-naturally occurring melanocortin analogs, relative to a control. In some embodiments, Cmax comprises a dose normalized Cmax (DNC max).

[0172] In some embodiments, the increased concentration is reflected by an increase in minimum plasma concentration (Cmin). An increase in Cmin may suggest increased absorption, reduced metabolism, or slower elimination of the non-naturally occurring melanocortin analogs, relative to a control. In some embodiments, Cmin comprises a dose normalized Cmin (DNCmin) .

[0173] In some embodiments, the increased concentration is reflected by a reduction in time to reach Cmax (Tmax). A reduced Tmax may suggest increased absorption, reduced-102-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO metabolism, or slower elimination of the non-naturally occurring melanocortin analogs, relative to a control.

[0174] In some embodiments, the increased concentration is reflected by a final measurable concentration (Tfinai). An increased Tfinai may suggest increased absorption, reduced metabolism, or slower elimination of the non-naturally occurring melanocortin analogs, relative to a control.

[0175] In some embodiments, the increased concentration is reflected by an increase in area under the curve (AUG). An increase in AUG may signify increased exposure to the non-naturally occurring melanocortin analogs and / or may suggest increased absorption, reduced metabolism, or slower elimination of the non-naturally occurring melanocortin analogs, relative to a control. The AUG measurement may comprise an Area Under the Curve for Concentration of Drug in Non-Compartmental Analysis (DNAUC).

[0176] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1 .5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after oral administration of the non- naturally occurring melanocortin analog.

[0177] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1 .5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after oral administration of the non- naturally occurring melanocortin analog.

[0178] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement at least about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after oral administration of the non-naturally occurring melanocortin analog.-103-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0179] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement during oral administration of the non-naturally occurring melanocortin analog.

[0180] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement at the completion of oral administration of the non- naturally occurring melanocortin analog.Additional pD and pK Embodiments

[0181] In some embodiments, the pharmaceutical compositions comprising a non- naturally occurring melanocortin analog of the present technology exhibits one or more of the following:(a) an increase in half-life relative to a control;(b) a reduction in clearance relative to a control;(c) an increase in tissue concentration relative to a control;(d) an increase in plasma concentration relative to a control;(e) an increase in serum concentration relative to a control;(f) an increase in distribution relative to a control;(g) an increase in an AUG measurement relative to a control;(h) an increase in a DNAUC measurement relative to a control;(i) an increase in Tfinai relative to a control;(j) an increase in Cmax relative to a control;(k) an increase in Cmin relative to a control;(l) an increase in DNCmin relative to a control;(m) an increase in MRT relative to a control;(n) an increase in Cavg relative to a control;(o) an increase in Ctrough relative to a control;-104-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO(p) an increase in CT relative to a control;(q) an increase in Vd relative to a control;(r) a reduction in Tmax relative to a control; or(s) a reduction in Q relative to a control.

[0182] In some embodiments, the pharmaceutical compositions comprising a non- naturally occurring melanocortin analog of the present technology exhibits one or more of the following, relative to a control:(a) an increase in half-life by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(b) a reduction in clearance by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;(c) an increase in tissue concentration by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(d) an increase in plasma concentration by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(e) an increase in serum concentration by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(f) an increase in distribution by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(g) an increase in an AUG by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% measurement relative to a control;-105-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO(h) an increase in a DNAUC measurement by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(i) an increase in Tfinai by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(j) an increase in Cmax by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(k) an increase in Cmin by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(l) an increase in DNCmin by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(m) an increase in MRT by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(n) an increase in Cavg by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(o) an increase in Ctrough by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(p) an increase in CT by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;-106-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO(q) an increase in Vd by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to a control;(r) a reduction in Tmax by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control; or(s) a reduction in Q by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control.

[0183] In some embodiments, the pharmaceutical compositions of the present technology increase a concentration of a non-naturally occurring melanocortin analog in the plasma and / or tissue of a subject, relative to a control.EXAMPLES

[0184] The following examples are intended to illustrate various embodiments of the present technology. As such, the specific embodiments discussed are not to be construed as limitations on the scope of the present technology. It will be apparent to one skilled in the art that various equivalents, changes, and modifications may be made without departing from the scope of present technology, and it is understood that such equivalent embodiments, are to be included herein. Further, all references cited herein are hereby incorporated by reference in their entirety, as if fully set forth herein.Example 1: Peptide Synthesis-Generic

[0185] The non-naturally occurring melanocortin analogs of the present technology were synthesized by conventional procedures (e.g., solution-phase procedure, solid-phase synthesis) for the formation of a peptide linkage between amino acids. The solution-phase procedure involved a condensation between the free alpha amino group of an amino acid or derivative thereof having the carboxyl group or other reactive groups protected and the free primary carboxyl group of another amino acid or derivative thereof having the amino group or other reactive groups protected. The solid-phase synthesis utilized a variety of resins and reagents and may involve additional purification steps.-107-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0186] The process for synthesizing the non-naturally occurring melanocortin analogs was generally performed by a procedure as follows. Each amino acid in the desired sequence of the non-naturally occurring melanocortin analogs was added one at a time in succession to another amino acid or derivative thereof or by a procedure whereby peptide fragments with the desired amino acid sequence were first synthesized conventionally and then condensed to provide the desired peptide. In most cases, the resulting peptide was then cyclized to yield a cyclic peptide.

[0187] Solid-phase peptide synthesis was carried out by sequentially incorporating the desired amino acid residues one at a time into the growing peptide chain coupled to a solidphase support according to the general principles of solid phase methods (see Merrifield, Angew Chem. 24:799-810 (1985) and Barany et al., The Peptides, Analysis, Synthesis and Biology, Vol. 2, Gross E. and Meienhofer J., Eds. Academic Press 1 -284 (1980)). An exemplary solid-phase synthesis of non-naturally occurring melanocortin analogs is provided below.

[0188] Initially, the C-terminal amino acid residue of the non-naturally occurring melanocortin analog was coupled to a support, e.g., a solid-phase or tag support. Coupling of the C-terminal amino acid residue and the solid-phase support may be carried out according to any method know in the art. Depending on the coupling method, the alphaamine of the C-terminal amino acid residue may or may not be protected with an amine protecting group, as described below. Likewise, the carboxyl group of the amino acid residue may or may not be activated prior to coupling to the solid-phase support in order to increase its electrophilicity. Some methods of coupling rely on the formation of an ester bond between the carboxyl group of the amino acid and a reactive handle on the solid-phase resin. For example, an amino acid residue may be coupled to a p-benzyloxybenzyl alcohol resin (Wang) or a 2-chlorotrityl chloride resin via an ester linkage. Some methods of coupling rely on the formation of an amide bond between the carboxyl group of the amino acid and a reactive handle on the solid-phase resin For example, an amino acid residue may be coupled to a benzhydrylamine (BHA) resin through an Fmoc-linker such as, for example, p- [(R,S)-a-[1 -(9H-fluor-en-9-yl)-methoxyformamido]-2,4-dimethyloxybenzyl]-phenoxyacetic acid (Rink linker) via an amide linkage.-108-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0189] The non-naturally occurring melanocortin analog was then synthesized by sequential amino acid addition or combination of peptide fragments. Subsequently, the peptide was cleaved from the solid-phase support and purified by methods known in the art, such as, for example, reverse phase high performance liquid chromatography (RP-HPLC) using a suitable column, such as a C18 column, or crystallization. Additionally, or alternatively, other methods of separation or purification were employed, including, but not limited to, methods based on the size or charge of the peptide. Once purified, the peptide was characterized by methods such as high-performance liquid chromatograph (HPLC), amino acid analysis, mass spectrometry, and the like.Example 2: Peptide Synthesis-Protecting Groups

[0190] During synthesis of the non-naturally occurring melanocortin analogs, reactive side chain groups of the various amino acid residues were protected with suitable protecting groups, which prevented undesirable chemical reaction from occurring at that site until the protecting group was removed.

[0191] Additionally, protection of the alpha amino group of an amino acid residue or fragment was performed while that entity reacting with the carboxyl group, followed by the selective removal of the alpha amino protecting group to allow a subsequent reaction to take place at that site. Specific protecting groups for solid phase synthesis methods and solution phase synthesis methods are known to those having ordinary skill in the art. Alpha amino groups were protected by a suitable protecting group, including a urethane-type protecting group, such as benzyloxycarbonyl (Z) and substituted benzyloxycarbonyl, such as p- chlorobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, p- biphenyl-isopropoxycarbonyl, 9-fluorenylmethoxycarbonyl (Fmoc) and p- methoxybenzyloxycarbonyl (Moz); aliphatic urethane-type protecting groups, such as t- butyloxycarbonyl (Boc), diisopropylmethoxycarbonyl, isopropoxycarbonyl, and allyloxycarbonyl. Fmoc was also used for alpha amino protection. Guanidino groups, if present, were protected by a suitable protecting group, such as nitro, p-toluenesulfonyl (Tos), Z, pentamethylchromanesulfonyl (Pmc), adamantyloxycarbonyl, pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) and Boc. Pmc was used as a protecting group for Arg.-109-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0192] Alpha aminoprotecting groups may be removed under basic conditions, such as, for example, using a solution of piperidine, piperazine, diethylamine, or morpholine (20- 40% v / v) in N,N-dimethylformamide (DMF). In synthesis methods in which alpha amino protecting groups were used, protecting groups were removed after synthesis of the peptide and before or after cleavage of the solid-phase support.Example 3: Peptide Synthesis-Additional Modifications

[0193] If necessary, the peptides were further modified to obtain N-terminus modifications, such as acetylation, while on resin, or were removed from the resin by use of a cleaving reagent and then modified. Likewise, C-terminus modification (e.g., amidation), was performed if needed.

[0194] Additionally, the cyclized peptide structures were obtained prior to cleavage from the peptide resin. For cyclization through reactive side chain moieties, the desired side chains were deprotected, and the peptide suspended in a suitable solvent and a cyclic coupling agent added. Suitable solvents, for example DMF, dichloromethane (DCM) or 1 - methyl-2-pyrrolidone (NMP), were used for the cyclization. Suitable cyclic coupling reagents (e.g., 2-(1 H-benzotriazol-1 -yl)-1 ,1 ,3,3-tetramethyluronium tetrafluoroborate (TBTU), 2-(1 H- benzotriazol-1 -yl)-1 ,1 ,3,3-tetramethyluronium hexafluorophosphate (HBTU), benzotriazole- 1 -yl-oxy-tris(dimethylamino)phosphoniumhexafluorophosphate (BOP), benzotriazole-1 -yl- oxy-tris(pyrrolidino)phosphoniumhexafluorophosphate (PyBOP), 2-(7-aza-1 H-benzotriazol- 1 -yl)-1 ,1 , 3, 3-tetramethyluronium tetrafluoroborate (TATU), 2-(2-oxo-1 (2H)-pyridyl)-1 ,1 ,3,3- tetramethyluronium tetrafluoroborate (TPTU), N,N'-dicyclohexylcarbodiimide / 1 - hydroxybenzotriazole (DCCI / HOBt)) were also used for the cyclization. Coupling was initiated by a suitable base, such as N,N-diispropylethylamine (DIPEA), sym-collidine or N- methylmorpholine (NMM).Example 4: Biological Data

[0195] The agonist and antagonist activity of exemplary non-naturally occurring melanocortin analogs at the melanocortin receptors (e.g., MC1 R, MC3R, MC4R, and MC5R) were measured via cAMP accumulation assay, according to the following procedure.-110-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOExperimental design and execution were conducted by Epics Therapeutics S.A. EuroscreenFast (Bruxelles, Belgium).Compound Handing

[0196] Compounds were delivered as powder (1 mg) or 10 mM solutions (100 pl) in 100% DMSO. Powders were solubilized in 100% DMSO at a concentration of 10 mM (master solution) in a defined solvent volume. Serial dilutions were performed from master solution in 100% DMSO to obtain intermediate concentrations 200-, 300- or 400-fold higher than the concentrations to be tested, depending on the assay. Each sample was diluted 100- fold in the assay buffer and dispensed in a test plate. Amounts, solvents, and dilutions were estimated based on standard small-molecule drugs. Cell lines used for functional assays are shown in Table 1 .Table 1. Cell linesCompound Testing

[0197] Compounds were tested for (i) agonist and / or antagonist activity at the human MC3 (FAST-0232C) and MC4 (FAST-0233C) receptors, (ii) agonist activity at the human MC1 (FAST-0230C) receptor, and / or (iii) agonist activity at the human MC5 (FAST-0233C) receptor at the following nanomolar concentrations, in duplicate: 0.0001 , 0.001 , 0.01 , 0.03, 0.1 , 0.3, 1 , 10, 100, and 1 ,000.Testing Protocol

[0198] Cyclic AMP (cAMP) Homogenous Time-Resolved Fluorescence (HTRF) assay for Gs coupled receptor:-111 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0199] CHO-K1 cells expressing recombinant human receptor grown prior to the test in media without antibiotic were detached by gentle flushing with PBS-EDTA (5 mM EDTA), recovered by centrifugation and resuspended in assay buffer (KRH: 5 mM KCI, 1.25 mM MgSO4, 124 mM NaCI, 25 mM HEPES, 13.3 mM Glucose, 1.25 mM KH2PO4, 1.45 mM CaCI2, 0.5 g / l BSA, supplemented with 1 mM IBMX or 25pM Rolipram).

[0200] Dose response curves were performed in parallel with the reference compounds.

[0201] For agonist test (384well): 5 pl of cells were mixed with 5 pl of the test compound at increasing concentrations and then incubated 30 min at room temperature. After addition of the lysis buffer containing cAMP-d2 and anti-cAMP cryptate detection reagents, plates were incubated 1 -hour at room temperature, and fluorescence ratios were measured according to the manufacturer specification, with the HTRF kit.

[0202] For antagonist test (384well): 5 pl of cells were mixed in the wells of an assay plate with 5 pl of a mix of test compound at increasing concentrations and reference agonist for a final concentration corresponding to the historical EC80. The plates were then incubated 30 min at room temperature. After addition of the lysis buffer containing cAMP-d2 and anti-cAMP cryptate detection reagents, plates were incubated 1 -hour at room temperature, and fluorescence ratios were measured according to the manufacturer specification, with the HTRF kit.Quality Control for Compound Testing

[0203] On each day of experimentation and prior to the testing of compounds, reference compounds were tested at several concentrations in duplicate (n=2) to obtain a dose-response curve and an estimated EC50 and / or IC50 values.

[0204] Reference values thus obtained for the test were compared to historical values obtained from the same receptor and used to validate the experimental session.

[0205] A session was considered as valid only if the reference value was found to be within a 0.5 logs interval from the historical value.-112-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0206] For replicate determinations, the maximum variability tolerated in the test was of + / -20% around the average of the replicates.Non-naturally Occurring Melanocortin Analog Grouping

[0207] Group A included non-naturally occurring melanocortin analogs A1 to A11 , all of which are cyclic peptides comprising the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) or a derivative thereof and cyclized through a lactam bond. Group A non-naturally occurring melanocortin analogs are provided in Table 2.Table 2. Group A non-naturally occurring melanocortin analogs

[0208] Group B included non-naturally occurring melanocortin analogs B1 to B32, all of which are cyclic peptides comprising the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a lactam bond between Asp and Lys. Group B melanocortin analogs include an N-terminal amino acid other than Nle and a C-terminal dVal-dPro moiety. Group B non-naturally occurring melanocortin analogs are provided in Table 3.Table 3. Group B non-naturally occurring melanocortin analogs-113-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-114-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0209] Group C included non-naturally occurring melanocortin analogs C1 to 022, all of which are cyclic peptides comprising the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a lactam bond between Asp and Lys. Group C melanocortin analogs include an N-terminal amino acid other than Nle and a C-terminal dTle-dPro moiety. Group C non-naturally occurring melanocortin analogs are provided in Table 4.Table 4. Group C non-naturally occurring melanocortin analogs-115-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0210] Group D included non-naturally occurring melanocortin analogs D1 to D27, all of which are cyclic peptides comprising a derivative of the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a lactam bond between Asp and Lys. Derivatives of the motif of SEQ ID NO: 387 included in Group D melanocortin analogs include substitution of Pro for another amino acid. Group D non-naturally occurring melanocortin analogs are provided in Table 5.Table 5. Group D non-naturally occurring melanocortin analogs-116-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0211] Group E included non-naturally occurring melanocortin analogs E1 to E15, all of which are cyclic peptides comprising a derivative of the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a lactam bond between Asp and Lys. Derivatives of the motif of SEQ ID NO: 387 included in Group E melanocortin analogs include substitution of Arg for another amino acid or substitution of Trp for another amino acid. Group E non-naturally occurring melanocortin analogs are provided in Table 6.Table 6. Group E non-naturally occurring melanocortin analogs-117-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0212] Group F included non-naturally occurring melanocortin analogs F1 to F50, all of which are cyclic peptides comprising the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a lactam bond between Asp and Lys. Group F melanocortin analogs include a C-terminal extension other than dVal-dPro. Group F non-naturally occurring melanocortin analogs are provided in Table 7.Table 7. Group F non-naturally occurring melanocortin analogs-118-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-119-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0213] Group G included non-naturally occurring melanocortin analogs G1 to G4, all of which are cyclic peptides comprising a derivative of the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a lactam bond between Asp and Lys. Group G melanocortin analog include a Pro or Gly after the Trp residue. Group G non-naturally occurring melanocortin analogs are provided in Table 8.Table 8. Group G non-naturally occurring melanocortin analogs

[0214] Group H included non-naturally occurring melanocortin analogs H1 to H10, all of which are cyclic peptides comprising a derivative of the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387) and cyclized through a disulfide bond. Group H non-naturally occurring melanocortin analogs are provided in Table 9.Table 9. Group H non-naturally occurring melanocortin analogs-120-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0215] Group I included non-naturally occurring melanocortin analogs 11 to I25, all of which are cyclic peptides comprising a derivative of the motif Trp-Pro-dPhe-Arg-Trp (SEQ ID NO: 391 ) or a derivative thereof. Derivatives of the motif of SEQ ID NO: may include substitution of T rp for another amino acid or substitution of Pro for another amino acid. Group I non-naturally occurring melanocortin analogs are provided in Table 10.Table 10. Group D non-naturally occurring melanocortin analogs-121 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0216] Group J included non-naturally occurring melanocortin analogs J1 to J7, all of which are cyclic peptides comprising a derivative of the motif Ala-His-dPhe-Arg-Trp (SEQ ID NO: 392) or a derivative thereof. Derivatives of the motif of SEQ ID NO: may include substitution of Ala for another amino acid, for example dAla. Group J non-naturally occurring melanocortin analogs are provided in Table 11 .Table 11. Group J non-naturally occurring melanocortin analogs-122-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0217] Group K included non-naturally occurring melanocortin analogs K1 to K16, all of which are cyclic peptides comprising a derivative of the motif Pro-dPhe-Arg-Trp (SEQ ID NO: 387). Group K melanocortin analogs include a C-terminal extension other than dVal- dPro and / or an N-terminus other than Nle. The C-terminus may comprise a dVal-dPro moiety with additional residues. Likewise, the N-terminus may comprise Nle with additional residues. Group K non-naturally occurring melanocortin analogs are provided in Table 12.Table 12. Group K non-naturally occurring melanocortin analogsAgonist activity of melanocortin analogs on melanocortin 1 and 5 receptors-123-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0218] Administration of some non-naturally occurring melanocortin analogs activated melanocortin 1 receptor (MC1 R) and / or melanocortin 5 receptor (MC5R) activity, as measured by cAMP levels (Table 13).Table 13. Dose-response results of melanocortin analogs and control against the melanocortin 1 receptor (MC1 R) and melanocortin 5 receptor (MC5R)-124-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-125-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-126-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-127-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO*** = < 1 nM** = 1 nM to 100 nM* = > 100 nMA — > 80% EmaxB = 50 - 80% EmaxC = < 50% Emax-128-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAgonist activity of melanocortin analogs on melanocortin 3 and 4 receptors

[0219] Administration of some non-naturally occurring melanocortin analogs activated melanocortin 3 receptor (MC3R) activity and / or melanocortin 4 receptor (MC4R) activity, as measured by cAMP levels (Table 14).Table 14. Dose-response results of melanocortin analogs and control against the melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R)-129-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-130-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-131 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-132-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO= < 1 nM** = 1 nM to 100 nM* = > 100 nMA — > 80% Emax-133-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOB = 50 - 80% EmaxC = < 50% EmaxAntagonist activity of melanocortin analogs on melanocortin 3 or 4 receptor

[0220] Administration of some non-naturally occurring melanocortin analogs inhibited melanocortin 3 receptor (MC3R) and / or melanocortin 4 receptor (MC4R) activity, as measured by cAMP levels (Table 15).Table 15. Dose-response results of melanocortin analogs and control against the melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R)-134-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-135-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-136-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-137-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO= < 1 nM** = 1 nM to 100 nM-138-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO* = > 100 nMA — > 80% EmaxB = 50 - 80% EmaxC = < 50% EmaxExample 5: Oral Formulations of Melanocortin Analogs

[0221] 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 2) was used as a comparator for the non-naturally occurring melanocortin analogs of the present technology because of the various conserved structural features between 010 and the exemplary melanocortin analogs. For example, 010 and the disclosed melanocortin analogs share one or more of the following features: N-terminal Nle, lactam cyclization, core His-dPhe-Arg-Trp (SEQ ID NO: 393) or His-p(F)dPhe-Arg-Trp (SEQ ID NO: 394) scaffolds or derivatives thereof, and C-terminal dVal-dPro or other degradation resistant moiety.

[0222] Several exemplary formulations of 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp- Orn]-dVal-dPro-NH2; SEQ ID NO: 2) with various permeation enhancers were prepared. The permeation enhancers tested included propyl gallate (PG), salcaprozate sodium (SNAG), sodium caprate (NaC10), sodium chenodeoxycholate (NaCDC), and soybean trypsin inhibitor (SBTI). Details of the exemplary formulations are provided in Table 16 below.Table 16. 010 Formulations

[0223] Exemplary formulations F1 , F3, F7, F9, F11 , F13, and F15 were administered to seven groups of fasted Male Sprague-Bawley (MSD) rats via the specifications provided in Table 17.Table 17. MSD Study Group Specifications-139-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0224] 010 plasma concentrations were assessed over a 24-hour period in each study group (Tables W and 19) (FIGS 1A-1 H).Table 18. PO1 -PO4 Plasma 010 Concentrations (ng / mL)Table 19. PO5-PO7 Plasma 010 Concentrations (ng / mL)-140-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0225] Pharmacokinetic (PK) parameters of 010 were also assessed in each group (Tables 20 and 21 ).Table 20. PO1 -PO4 PK ParametersTable 21 . PO5-PO7 PK Parameters|-141 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0226] Formulation F13, which included 30 mg propyl gallate, was found to increase 010 exposure in rats more than all other permeation enhancers and 010 alone. Total 010 exposure was increased by more than 20-fold in rats administered F13 relative to F1 , F3, F7, F9, and F1 1 , and by more than 10-fold in rats administered F13 relative to F15, as shown in Table 22 and FIGS. 2A and 2B.Table 22. Comparison of PK Parameters of 010 Formulations in Rats-142-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0227] 010 formulations with increasing amounts of propyl gallate were assessed in rats, dogs, and cynomolgus monkeys(FIG. 3). Formulations for rats included 40 mg / kg 010, formulations for dogs included 10 mg / kg 010, and formulations for cynomolgus monkeys included 5 mg / kg 010. Formulation and PK details are shown in Tables 23-25.Table 23. 40 mg / kg 010 Formulations and PK in RatsTable 24. 10 mg / kg 010 Formulations and PK in DogsTable 25. 5 mg / kg 010 Formulations and PK in Cynomolgus Monkeys

[0228] Based on the PK data collected from the above formulations, oral 010 formulations with 30 mg propyl gallate were then assessed male cynomolgus monkeys. The cynomolgus monkeys were fasted and then orally administered 5 mg / kg 010 formulated in one of the three study groups listed in Table 26.Table 26. 5 mg / kg 010 Formulations in Cynomolgus Monkeys-143-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0229] 010 plasma and cerebral spinal fluid (CSF) concentrations were assessed over a 24-hour period in each treatment group (Tables 27 and 28) (FIGS. 4A-4C).Table 27. Cynomolgus Monkey Plasma 010 Concentrations-144-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOND = Not determined; CSF Concentration (ng / mL) = CSF Concentration (ng / mL) x 1 (dilution factor); CSF / Plasma Ratio = CSF Concentration (ng / mL) I Plasma Concentration (ng / mL)

[0230] Pharmacokinetic (PK) parameters of 010 were also assessed in each group (Table 29).Table 29. Cynomolgus Monkey 010 PK DataND = Not determined (Parameters not determined due to inadequately defined termina elimination phase); If the adjusted rsq (linear regression coefficient of the concentration value on the terminal phase) is less than 0.9, T1 / 2 might not be accurately estimated; If the-145-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO% AUCExtra > 20%, AUCo-inf, Cl, M RTo-inf and Vdss might not be accurately estimated; If the % AUMCExtra > 20%, MRTo-inf and Vdss might not be accurately estimated; The adjusted linear regression coefficient of the concentration value on the terminal phase is less than 0.9, T1 / 2 might not be accurately estimated;a:AUC Ratio = Tissue AUCo-iast / Plasma AUCo- last.

[0231] Two monkeys showed concentrations in CSF above the lower limit of quantification (2 ng / mL). Individual monkey C3002 (FIG. 5) did not observe any CSF concentrations of 010 above the lower limit of quantification. C3002 also had the lowest Cmax of all three individuals.

[0232] Based on the mean CSF / plasma ratio for C3001 and C3003 at 1 and 2 hours, it’s not expected for the plasma concentration of C3002 to produce CSF concentration above the lower limit of quantification of 2 ng / mL at those same time points (Tables 30 and 31 ).Table 30. PO3 010 ConcentrationTable 31. PO3 010 Pharmacokinetics-146-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0233] These data demonstrated that 010 is found in the CSF of monkeys following oral administration of 010 with propyl gallate.Example 6: Assessing Oral Bioavailabilitv without Formulation Enhancers

[0234] Oral formulations of four exemplary melanocortin agonists, A07D (A4; Ac-Nle- c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2; SEQ ID NO: 3), K11 (Ac-dLys-c[Asp-Pro- dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2; SEQ ID NO: 4), 07 (Ac-Nle-c[Glu-Pro-p(F)dPhe- Arg-Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 5), and 010 (Ac-Nle-c[Glu-His-p(F)dPhe-Arg- Trp-Orn]-dVal-dPro-NH2; SEQ ID NO: 2), without formulation enhancers were than assessed in male cynomolgus monkeys. Cynomolgus monkeys were orally administered 10 mg / kg or 30 mg / kg A07D; 10 mg / kg or 30 mg / kg 07; 3 mg / kg, 10 mg / kg, 30 mg / kg, or 60 mg / kg 010; or 10 mg / kg or 30 mg / kg 03 in accordance with procedures of the present technology. Plasma concentrations up to 24 hours after administration are shown in FIGS. 6A-6D.A07D

[0235] Various pharmacokinetic parameters of A07D were assessed in the plasma of male cynomolgus monkeys fasted prior to dosing A07D at 10 mg / kg and 30 mg / kg orally. Results are shown in Table 32 and FIG. 6A.Table 32. Oral Bioavailability Data for Exemplary Melanocortin Analog A07D-147-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO-148-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOND = Not determined (Parameters not determined due to inadequately defined termina elimination phase).BQL = Below the lower limit of quantitation (LLOQ).If the adjusted rsq (linear regression coefficient of the concentration value on the terminal phase) is less than 0.9, T1 / 2 might not be accurately estimated.If the % AUCExtra > 20%, AUCo-inf, Cl, M RTo-inf and Vdss might not be accurately estimated.If the % AUMCExtra > 20%, MRTo-inf and Vdss might not be accurately estimated.The adjusted linear regression coefficient of the concentration value on the terminal phase is less than 0.9, T1 / 2 might not be accurately estimated. a: Bioavailability (%) was calculated using AUCo-inf (if all AUCExtra 20%) or AUCo-iast (if one or more AUCExtra > 20%) with Nominal Dose.03, 07, & 010

[0236] Plasma concentration of 03, 07, and 010 were next assessed up to 24 hours following oral administration to cynomolgus monkeys at 10 mg / kg or 30 mg / kg, results of which are shown in FIGS. 6B-6D.

[0237] FIG. 6B demonstrates the oral bioavailability of low doses of 07, with plasma concentrations of about 10 ng / mL of 07 up to 8 hours after oral administration. Similarly, FIG. 6C demonstrates the oral bioavailability of low doses of 03, with plasma concentrations of greater than 10 ng / mL of 03 up to 8 hours after oral administration. Additionally, monkeys administered 07 and 03 at 30 mg / kg doses exhibited plasma concentration of at least about 5 ng / mL up to 24 hours after oral administration.

[0238] As shown in FIG. 6D, monkeys orally administered 60 mg / kg 010 exhibited plasma concentrations above 10 ng / mL at 16-18 hours after administration. Further, monkeys orally administered 10 mg / kg 010 exhibited similar plasma concentrations to-149-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO monkeys orally administered 30 mg / kg 010 at 8 hours post administration (> 10 ng / mL), demonstrating the oral bioavailability of 010 at low doses.Additional Embodiments

[0239] Various embodiments of the present technology are set forth below in paragraphs

[0240] to

[0321] :

[0240] 1. An orally deliverable pharmaceutical composition comprising a non- naturally occurring melanocortin analog, the melanocortin analog comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 , 2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);-150-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen,-151 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’) and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0241] 2. A pharmaceutical composition comprising a non-naturally occurring melanocortin agonist and a permeation enhancer, the non-naturally occurring melanocortin agonist comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) ,-152-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;-153-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when-154-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0242] 3. A pharmaceutical composition for oral administration of a non-naturally occurring melanocortin agonist, the composition comprising a permeation enhancer and a non-naturally occurring melanocortin analog comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);-155-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;-156-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr--157-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOPro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0243] 4. A pharmaceutical composition formulated to deliver about 0.1 mg / kg to about 5 mg / kg, per body weight of a subject, of a non-naturally occurring melanocortin agonist to the subject, the pharmaceutical composition comprising: a permeation enhancer; and a non-naturally occurring melanocortin agonist comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5--158-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn;-159-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.-160-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0244] 5. The pharmaceutical composition of any one of embodiments 1 -4, wherein the non-naturally occurring melanocortin analog is present at a concentration of about 0.01 mg / mL to about 200 mg / mL.

[0245] 6. The pharmaceutical composition of any one of embodiments 1 -5, wherein the non-naturally occurring melanocortin analog is present at a concentration of about 0.1 mg / mL to about 100 mg / mL.

[0246] 7. The pharmaceutical composition of any one of embodiments 1 -6, wherein the non-naturally occurring melanocortin analog is present at a concentration of about 0.1 mg / mL to about 5 mg / mL.

[0247] 8. The pharmaceutical composition of any one of embodiments 1 -7, wherein the non-naturally occurring melanocortin analog is present in an amount of about 1 .0 mg to about 20 g.

[0248] 9. The pharmaceutical composition of any one of embodiments 1 -8, wherein the non-naturally occurring melanocortin analog is present in an amount of about 10 mg to about 1500 mg.

[0249] 10. The pharmaceutical composition of any one of embodiments 1 -9, wherein the permeation enhancer is present at a concentration of about 0.1 mg / mL to about 25 mg / mL.

[0250] 11. The pharmaceutical composition of any one of embodiments 1 -10, wherein the permeation enhancer is present at a concentration of about 6 mg / mL.

[0251] 12. The pharmaceutical composition of any one of embodiments 1 -11 , wherein the permeation enhancer is present in an amount of about 10 mg to about 3000 mg.

[0252] 13. The pharmaceutical composition of any one of embodiments 1 -12, further comprising water.

[0253] 14. The pharmaceutical composition of any one of embodiments 1 -13, formulated for oral delivery.

[0254] 15. The pharmaceutical composition of embodiment 14, formulated as an oral dosage unit.-161 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0255] 16. The pharmaceutical composition of embodiment 15, wherein the oral dosage unit is a tablet or a capsule.

[0256] 17. The pharmaceutical composition of embodiment 16, wherein the capsule is a liquid-filled capsule or a semi-solid-filled capsule.

[0257] 18. The pharmaceutical composition of any one of embodiments 1 -17, further comprising an excipient.

[0258] 19. The pharmaceutical composition of embodiment 18, wherein the excipient comprises or consists of an enzyme inhibitor.

[0259] 20. The pharmaceutical composition of embodiment 18 or 19, wherein the excipient may comprise one or more compounds which inhibit, bind, or otherwise target an enzyme comprising a phosphatase or a protease.

[0260] 21. The pharmaceutical composition of embodiment 20, wherein the phosphatase is an intestinal phosphatase.

[0261] 22. The pharmaceutical composition of embodiment 20, wherein the protease is selected from the group consisting of a metalloprotease, an endopeptidase, and an amino peptidase.

[0262] 23. The pharmaceutical composition of embodiment 20 or 22, wherein the protease is selected from the group consisting of a trypsin, a trypsin-like protease, a chymotrypsin, an elastase, a pepsin, a mesotrypsin, a tryptase, and a chymase.

[0263] 24. The pharmaceutical composition of any one of embodiments 19-23, wherein the enzyme inhibitor is a protease inhibitor.

[0264] 25. The pharmaceutical composition of any one of embodiments 23-24, wherein the enzyme inhibitor is an intestinal enzyme inhibitor.

[0265] 26. The pharmaceutical composition of any one of embodiments 19-25, wherein the enzyme inhibitor is selected from the group consisting of sodium fluoride, ethylenediaminetetraacetic acid (EDTA), aprotinin, pepstatin, bestatin, bacitracin, boric acid, a soybean trypsin inhibitor (SBTI), a Bowman-Birk inhibitor (BBI), and a Kunitz trypsin inhibitor (KTI).-162-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0266] 27. The pharmaceutical composition of any one of embodiments 1 -26, wherein the non-naturally occurring melanocortin analog comprises a sequence of Formula (I), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 , 2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;-163-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-dPhe-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 6);Ac-Nle-c[Asp-dTyr-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 7);Ac-Nle-c[Asp-dGln-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 8);Ac-Nle-c[Asp-dTrp-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 9);-164-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Phe-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 10);Ac-Nle-c[Asp-Bip-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 11 );Ac-Nle-c[Asp-Trp-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 12);Ac-Nle-c[Asp-Tyr-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 13);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 14);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 15);Ac-Nle-c[Glu-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 16);Ac-Nle-c[Asp-dHis-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 17);Ac-Nle-c[Asp-Gln-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 18);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 19);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-NH2(SEQ ID NO: 20);Ac-Nle-c[Asp-Pro-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 21 );Ac-Arg-c[Asp-Pro-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 22);Ac-Nle-c[Asp-Trp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 23);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 24);Ac-Nle-c[Glu-Pro-p(CI)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 25);Ac-Ala-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 26);Ac-Ala-c[Glu-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 27);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 28);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 29);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 30);Ac-dAla-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 31 );Ac-Ala-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 32);Ac-Ala-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 33);-165-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Glu-Trp-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 34);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 35);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 36);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 37);Ac-Nle-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 38);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 39);Ac-Nle-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 38);Ac-Arg-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 40);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 41 );Ac-Nle-c[Glu-His-p(CI)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 42);Ac-Nle-c[Cys-His-p(CI)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 43);Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 44);Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 45);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 46);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 47);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 5);Ac-Nle-c[Asp-dTyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 48);Ac-Nle-c[Asp-dPhe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 49);Ac-Nle-c[Asp-dTrp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 50);Ac-Nle-c[Asp-Trp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 51 );Ac-Nle-c[Asp-Tyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 52);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 2);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);-166-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 60);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 61 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-Trp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 74);Ac-Nle-c[Glu-Trp-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 75);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 76);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 77);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 78);-167-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Glu-His-p(F)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 79);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 80);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 81 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 82);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 83);Ac-dOrn-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 84);Ac-dPhe-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 85);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 86);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 89);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 90);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-dAla-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 94);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 95);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97);Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2 (SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2 (SEQ ID NO: 102);-168-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2 (SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2 (SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2 (SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2 (SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-dHis-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 120);Ac-Nle-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 121 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 124);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);-169-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 118);Ac-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2 (SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 142);Ac-Arg-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 143);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 144);Ac-Lys-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 145);Ac-His-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 146);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);-170-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 149);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 150);Ac-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 151 );Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2 (SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2 (SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.-171 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO

[0267] 28. The pharmaceutical composition of any one of embodiments 1 -27, wherein the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 , 2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));-172-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated,-173-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

[0268] 29. The pharmaceutical composition of any one of embodiments 1 -28, wherein the non-naturally occurring melanocortin analog comprises a sequence of Formula (IA), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 , 2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine-174-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO(Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys;-175-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-dTyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 48);Ac-Nle-c[Asp-dPhe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 49);Ac-Nle-c[Asp-dTrp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 50);Ac-Nle-c[Asp-Trp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 51 );Ac-Nle-c[Asp-Tyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 52);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 60);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 61 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);-176-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 73);Ac-Nle-c[Asp-Trp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 74);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 76);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 78);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 80);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 81 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 82);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 83);Ac-dOrn-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 84);Ac-dPhe-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 85);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 89);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 90);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPr...

Claims

Docket No.: 183B-412978-WOCLAIMS l / We claim:

1. An orally deliverable pharmaceutical composition comprising a non-naturally occurring melanocortin analog, the melanocortin analog comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);-216-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that:-217-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’) and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

2. A pharmaceutical composition comprising a non-naturally occurring melanocortin agonist and a permeation enhancer, the non-naturally occurring melanocortin agonist comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:-218-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOX1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp,-219-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOD-hydroxy proline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated,-220-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

3. A pharmaceutical composition for oral administration of a non-naturally occurring melanocortin agonist, the composition comprising a permeation enhancer and a non-naturally occurring melanocortin analog comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);-221 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;-222-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is-223-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOLys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

4. A pharmaceutical composition formulated to deliver about 0.1 mg / kg to about 5 mg / kg, per body weight of a subject, of a non-naturally occurring melanocortin agonist to the subject, the pharmaceutical composition comprising: a permeation enhancer; and a non-naturally occurring melanocortin agonist comprising a sequence of Formula (I):X1-X2-X3- R1- R2- R3- R4- R5- R6-R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I ) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one-224-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO(Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn;-225-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(CI)dPhe, then R2is dCys, Asp, or Glu, R3is Aba, Aia, Ata, or His, R1is not Ala or dAla, R5is Arg, R6is Trp, and Y1is not Arg or dArg, wherein when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle, when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.-226-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO5. The pharmaceutical composition of any one of claims 1 -4, wherein the non- naturally occurring melanocortin analog is present at a concentration of about 0.01 mg / mL to about 200 mg / mL.

6. The pharmaceutical composition of any one of claims 1 -5, wherein the non- naturally occurring melanocortin analog is present at a concentration of about 0.1 mg / mL to about 100 mg / mL.

7. The pharmaceutical composition of any one of claims 1 -6, wherein the non- naturally occurring melanocortin analog is present at a concentration of about 0.1 mg / mL to about 5 mg / mL.

8. The pharmaceutical composition of any one of claims 1 -7, wherein the non- naturally occurring melanocortin analog is present in an amount of about 1 .0 mg to about 20 g-9. The pharmaceutical composition of any one of claims 1 -8, wherein the non- naturally occurring melanocortin analog is present in an amount of about 10 mg to about 1500 mg.

10. The pharmaceutical composition of any one of claims 1 -9, wherein the permeation enhancer is present at a concentration of about 0.1 mg / mL to about 25 mg / mL.

11. The pharmaceutical composition of any one of claims 1 -10, wherein the permeation enhancer is present at a concentration of about 6 mg / mL.

12. The pharmaceutical composition of any one of claims 1 -1 1 , wherein the permeation enhancer is present in an amount of about 10 mg to about 3000 mg.

13. The pharmaceutical composition of any one of claims 1 -12, further comprising water.-227-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO14. The pharmaceutical composition of any one of claims 1 -13, formulated for oral delivery.

15. The pharmaceutical composition of claim 14, formulated as an oral dosage unit.

16. The pharmaceutical composition of claim 15, wherein the oral dosage unit is a tablet or a capsule.

17. The pharmaceutical composition of claim 16, wherein the capsule is a liquid- filled capsule or a semi-solid-filled capsule.

18. The pharmaceutical composition of any one of claims 1 -17, further comprising an excipient.

19. The pharmaceutical composition of claim 18, wherein the excipient comprises or consists of an enzyme inhibitor.

20. The pharmaceutical composition of claim 18 or 19, wherein the excipient may comprise one or more compounds which inhibit, bind, or otherwise target an enzyme comprising a phosphatase or a protease.

21. The pharmaceutical composition of claim 20, wherein the phosphatase is an intestinal phosphatase.

22. The pharmaceutical composition of claim 20, wherein the protease is selected from the group consisting of a metalloprotease, an endopeptidase, and an amino peptidase.-228-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO23. The pharmaceutical composition of claim 20 or 22, wherein the protease is selected from the group consisting of a trypsin, a trypsin-like protease, a chymotrypsin, an elastase, a pepsin, a mesotrypsin, a tryptase, and a chymase.

24. The pharmaceutical composition of any one of claims 19-23, wherein the enzyme inhibitor is a protease inhibitor.

25. The pharmaceutical composition of any one of claims 23-24, wherein the enzyme inhibitor is an intestinal enzyme inhibitor.

26. The pharmaceutical composition of any one of claims 19-25, wherein the enzyme inhibitor is selected from the group consisting of sodium fluoride, ethylenediaminetetraacetic acid (EDTA), aprotinin, pepstatin, bestatin, bacitracin, boric acid, a soybean trypsin inhibitor (SBTI), a Bowman-Birk inhibitor (BBI), and a Kunitz trypsin inhibitor (KTI).

27. The pharmaceutical composition of any one of claims 1 -26, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (I), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);-229-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is selected from the group consisting of Phe, dPhe, para-fluoro-D-phenylalanine (p(F)dPhe), and para-chloro-D-phenylalanine (p(CI)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen;R8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;-230-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe or p(CI)dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-dPhe-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 6);Ac-Nle-c[Asp-dTyr-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 7);Ac-Nle-c[Asp-dGln-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 8);Ac-Nle-c[Asp-dTrp-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 9);Ac-Nle-c[Asp-Phe-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 10);Ac-Nle-c[Asp-Bip-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 11 );Ac-Nle-c[Asp-Trp-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 12);Ac-Nle-c[Asp-Tyr-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 13);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 14);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 15);Ac-Nle-c[Glu-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 16);Ac-Nle-c[Asp-dHis-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 17);Ac-Nle-c[Asp-Gln-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 18);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 19);-231 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-NH2(SEQ ID NO: 20);Ac-Nle-c[Asp-Pro-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 21 );Ac-Arg-c[Asp-Pro-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 22);Ac-Nle-c[Asp-Trp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 23);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 24);Ac-Nle-c[Glu-Pro-p(CI)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 25);Ac-Ala-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 26);Ac-Ala-c[Glu-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 27);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 28);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 29);Ac-Nle-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 30);Ac-dAla-c[Asp-Pro-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 31 );Ac-Ala-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 32);Ac-Ala-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 33);Ac-Nle-c[Glu-Trp-Pro-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 34);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 35);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 36);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 37);Ac-Nle-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 38);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 39);Ac-Nle-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 38);Ac-Arg-c[Asp-His-p(CI)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 40);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 41 );Ac-Nle-c[Glu-His-p(CI)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 42);-232-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Cys-His-p(CI)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 43);Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 44);Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 45);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 46);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 47);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 5);Ac-Nle-c[Asp-dTyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 48);Ac-Nle-c[Asp-dPhe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 49);Ac-Nle-c[Asp-dTrp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 50);Ac-Nle-c[Asp-Trp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 51 );Ac-Nle-c[Asp-Tyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 52);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 2);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 60);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 61 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);-233-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-Trp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 74);Ac-Nle-c[Glu-Trp-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 75);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 76);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 77);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 78);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 79);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 80);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 81 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 82);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 83);Ac-dOrn-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 84);Ac-dPhe-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 85);Ac-Nle-c[Glu-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 86);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);-234-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 89);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 90);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-dAla-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 94);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 95);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97);Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2(SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2(SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2(SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1 ')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);-235-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2 (SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-dHis-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 120);Ac-Nle-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 121 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 124);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 118);Ac-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 133);-236-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2 (SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 142);Ac-Arg-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 143);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 144);Ac-Lys-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 145);Ac-His-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 146);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 149);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 150);Ac-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 151 );Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);-237-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2 (SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2 (SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2 (SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2 (SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.

28. The pharmaceutical composition of any one of claims 1 -27, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (IA):X1-X2-X3- R1- R2- R3- R4- R5- R6- R7- R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A) , wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);-238-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and-239-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is p(F)dPhe, then R3is Pro, His, dHis, Gin, dGIn, Phe, or Bip, R6is not dTrp, and Y1is dVal, dPro, or dTle, wherein when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R1is not dAla, R2is not Cys, R6is Trp, Y2is not dTle, Y4-Y7are absent, and the C-terminus is amidated, when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn, when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.-240-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO29. The pharmaceutical composition of any one of claims 1 -28, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (I A), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 , 2,3,4- tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp- Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D- phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5- tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5- a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), glutamine (Gin), and D-glutamine (dGIn);R4is dPhe or para-fluoro-D-phenylalanine (p(F)dPhe);R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;-241 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu, R4is dPhe, and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-dTyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 48);Ac-Nle-c[Asp-dPhe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 49);Ac-Nle-c[Asp-dTrp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 50);Ac-Nle-c[Asp-Trp-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 51 );Ac-Nle-c[Asp-Tyr-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 52);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);-242-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 60);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 61 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-Trp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 74);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 76);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 78);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 80);-243-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 81 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 82);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 83);Ac-dOrn-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 84);Ac-dPhe-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 85);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 89);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 90);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-dAla-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 94);Ac-Nle-c[Glu-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 95);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97);Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2(SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2(SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2(SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);-244-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1 ')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2(SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2(SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-dHis-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 120);Ac-Nle-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 121 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 124);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);-245-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 142);Ac-Arg-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 143);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 144);Ac-Lys-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 145);Ac-His-c[Asp-Gln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 146);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 149);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 150);-246-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 151 );Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.

30. The pharmaceutical composition of any one of claims 1 -29, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (I A(i)) :X1-X2-X3- R1- R2- R3- R4- R5- R6- R7-R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7( I A(i)) , wherein:-247-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOX1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanylhistidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp- Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe- Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4- amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine- 4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));R7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);-248-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R4is dPhe, R1is Nle, and R3is Pro, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R4is dPhe, R1is Nle, and R3is not Pro, then (i) R3is selected from loc, Aba, Aia, Ata, APC, APPC, Ala, Hyp, dPhe, dGIn, Trp, dTrp, Tyr, dTyr, Ate, Trp-Ala, Trp-Leu, Tyr- Pro, dPhe-Pro, dTyr-Pro, Phe-His, Leu, Tic, and Bip and R7is Lys, (ii) R3is His, R6is Trp, Y1is dVal, Y3-Y7are absent, and either (a) R5is transPro(guan) or cisPro(guan) and R7is Lys, or (b) R5is Arg and R7is Pro, or (iii) R3is Pro-His or Trp-Pro, R5is Arg, R6is not Phe, or Nal (1 ’), and R7is not dCys or Orn,-249-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO when R4is dPhe, and R1is not Nle, then R3is Pro, Trp-Pro, or Ala-His, and the C- terminus is amidated, wherein when R3is Pro, then (a) the N-terminus is not acetylated when R1is Phe, dPhe, or Trp, and (b) Y2is dPro when R1is dAla, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

31. The pharmaceutical composition of any one of claims 1 -30, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (I A(i)), wherein:X1is absent or norlecuine (Nle);X2is absent, phenylalanine (Phe), or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, proline (Pro), leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanylhistidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp- Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe- Pro), alanine (Ala), hydroxyproline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4- amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 -amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine- 4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), 2’-naphthylalanine (Nal(2’)), and 2’-D-naphthylalanine (dNal(2’));-250-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR7is selected from the group consisting of glycine (Gly), Pro, Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, dLeu, Ala, D-alanine (dAla), Gly, Hyp, D-hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D- threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );-251 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2 (SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2 (SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2 (SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2 (SEQ ID NO: 109);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(1')-Lys]-dVal-dPro-NH2(SEQ ID NO: 110);Ac-Nle-c[Asp-Trp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 111 );Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 113);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 114);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 115);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2 (SEQ ID NO: 116);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2(SEQ ID NO: 117);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 118);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 112);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 122);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 123);Ac-Nle-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 124);Ac-Nle-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 125);Ac-Nle-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 126);-252-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 113);Ac-Nle-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 118);Ac-Nle-c[Glu-Trp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 127);Ac-Nle-c[Asp-His-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2(SEQ ID NO: 128);Ac-Nle-c[Glu-His-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 129);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 130);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dArg-NH2(SEQ ID NO: 131 );Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 142);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 144);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 148);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 149);Ac-Arg-c[Asp-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 150);Ac-Arg-c[Asp-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 151 );-253-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-Pro-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 152);Ac-Arg-c[Asp-His-dPhe-His-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 153);Ac-Arg-c[Glu-Pro-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 154);Ac-Arg-c[Glu-His-dPhe-His-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 155);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 162);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 163);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam or disulfide bond.

32. The pharmaceutical composition of any one of claims 1 -31 , wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (IA(ii)): X1-X2-X3-R1-R2-R3-R4-R5-R6-R7-R8-Y1-Y2-Y3-Y4-Y5-Y6-Y7(IA(ii)), wherein:X1is absent or norlecuine (Nle);-254-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOX2is absent or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is proline (Pro);R4is dPhe;R5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, T- naphthylalanine (Nal(1 ’)), and 2’-naphthylalanine (Nal(2’));R7is selected from the group consisting of glycine (Gly), Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, Ala, D-alanine (dAla), Gly, Hyp, D- hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D-threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of:-255-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO a lactam bond between R2and R8, when R2is Asp, R7is Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7or R8is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R1is Nle, then R2is not Cys, R6is not dNal(2’), the N-terminus is acetylated, and either (i) Y1is dVal, Y4is not dAsp, and X1-X3are all absent or all Nle, wherein when R2is Glu, then R6is Trp and the C-terminus is amidated, or (ii) Y1is not dVal, wherein when Y1is Asp, then Y2is dPro, when Y1is Lys, then Y2is not Vai, when Y1is dLys, then Y2is not dPro, and when Y1is dThr, then the C-terminus is not amidated, when R1is not Nle, then the C-terminus is amidated, wherein when R1is Phe, dPhe, or Trp, then the N-terminus is not acetylated, and when R1is dAla, then Y2is dPro, and when Y1is dAsp, dAla, or Gly, then Y3-Y7are absent.

33. The pharmaceutical composition of any one of claims 1 -32, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (IA(ii)), wherein:X1is absent or norlecuine (Nle);X2is absent or Nle;X3is absent or Nle;R1is selected from the group consisting of Nle, Phe, D-phenylalanine (dPhe), alanine (Ala), D-alanine (dAla), arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), D-histidine (dHis), ornithine (Orn), D-ornithine (dOrn), D-leucine (dLeu), D- tyrosine (dTyr), tryptophan (Trp), and D-tryptophan (dTrp);R2is selected from the group consisting of aspartic acid (Asp), D-aspartic acid (dAsp), glutamic acid (Glu), D-penicillamine (dPen), cysteine (Cys), and D-cysteine (dCys);R3is proline (Pro);R4is dPhe;-256-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR5is selected from the group consisting of Arg, His, Lys, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, dTrp, Phe, Aia, Aba, Ata, 1 ’- naphthylalanine (Nal(1 ’)), and 2’-naphthylalanine (Nal(2’));R7is selected from the group consisting of glycine (Gly), Lys, dLys, Orn, Cys, dCys, and dPen; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), valine (Vai), D-proline (dPro), Pro, D-tertleucine (dTle), dArg, Arg, dLys, Lys, Ala, D-alanine (dAla), Gly, Hyp, D- hydroxyproline (dHyp), Trp, asparagine (Asn), D-asparagine (dAsn), Asp, dAsp, D-threonine (dThr), p-proline (pPro);Y2is absent or selected from the group consisting of dVal, Vai, dPro, Pro, Hyp, dHyp, dAla, Ala, Gly, Asp, dAsn, dTle, dArg, p2-valine (p2Val), p3-valine (p3Val), and pPro;Y3is absent or selected from the group consisting of dVal, Vai, dPro, Pro, dLys, Lys, and dThr;Y4is absent or selected from the group consisting of dVal, dPro, Asp, and dAsp;Y5is absent or dVal;Y6is absent or dVal;Y7is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7or R8is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:-257-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Cys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 98);Ac-Nle-c[Asp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 99);Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 100);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 101 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Val-Pro-NH2(SEQ ID NO: 102);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-NH2(SEQ ID NO: 103);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-NH2(SEQ ID NO: 104);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 105);Ac-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 106);Ac-Nle-c[Glu-Pro-dPhe-Arg-dTrp-Orn]-dVal-dPro-NH2(SEQ ID NO: 107);Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-OH (SEQ ID NO: 108);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 109);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 136);Ac-Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 137);Ac-Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 138);Ac-dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2(SEQ ID NO: 139);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 140);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 141 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 159);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 160);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 161 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 162); andAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 163),-258-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO wherein c represents cyclization through a lactam or disulfide bond.

34. The pharmaceutical composition of any one of claims 1 -31 , wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (I A(iii)) :X1-X2- R1- R2- R3- R4- R5- R6- R7- R8-Y1- Y2- Y3-Y4( I A(i i i ) ) , wherein:X1is absent or norlecuine (Nle);X2is absent or phenylalanine (Phe);R1is selected from the group consisting of Nle, Phe, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His), tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxy proline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8- dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6- tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 - amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of Pro, Lys, and Cys; andR8is absent or Lys;-259-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOY1is selected from the group consisting of D-valine (dVal), D-tertleucine (dTle), dArg, dLys, and dLeu;Y2is absent or selected from the group consisting of dVal, dPro, and dHyp;Y3is absent or dVal;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that: when R3is His, then R1is Nle, and either (i) R7is Pro or (ii) R5is transPro(guan) or cisPro(guan), and when R3is Hyp, then R7is not Pro.

35. The pharmaceutical composition of any one of claims 1 -31 and 34, wherein the non-naturally occurring melanocortin analog comprises a sequence of Formula (I A(iii)), wherein:X1is absent or norlecuine (Nle);X2is absent or phenylalanine (Phe);R1is selected from the group consisting of Nle, Phe, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, Phe, dPhe, Trp, dTrp, tyrosine (Tyr), dTyr, leucine (Leu), biphenylalanine (Bip), 1 ,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), prolyl-histidine (Pro-His), alanyl-histidine (Ala-His), phenylalanyl-histidine (Phe-His),-260-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO tryptyl-alanine (Trp-Ala), tryptyl-leucine (Trp-Leu), tryptyl-proline (Trp-Pro), tyrosyl-proline (Tyr-Pro), D-tyrosyl-proline (dTyr-Pro), D-phenylalanyl-proline (dPhe-Pro), alanine (Ala), hydroxy proline (Hyp), 4-amino-1 ,2,4,5-tetrahydro-2-benzazepin-3-one (Aba), 7-amino-7,8- dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)-one (Ata), 4-amino-1 ,4,5,6- tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia), 2-aminotetraline-2-carboxylic acid (Ate), 1 - amino-4-phenylcyclohexane-carboxylic acid (APC), 4-aminophenylpiperidine-4-carboxylic acid (APPC), indoline-2-carboxylic acid (loc), and D-glutamine (dGIn);R4is dPhe;R5is selected from the group consisting of Arg, trans-4-guanidyl-proline (transPro(guan)), and cis-4-guanidyl-proline (cisPro(guan));R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of Pro, Lys, and Cys; andR8is absent or Lys;Y1is selected from the group consisting of D-valine (dVal), D-tertleucine (dTle), dArg, dLys, and dLeu;Y2is absent or selected from the group consisting of dVal, dPro, and dHyp;Y3is absent or dVal;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R8, when R2is Asp, R7is Pro or Gly, and R8is Lys; a lactam bond between R2and R7, when R2is Asp or dAsp and R7is Lys, dLys, or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys or dPen and R7is selected from the group consisting of Cys, dCys, and dPen, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2 (SEQ ID NO: 115);-261 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 119);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 132);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 133);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 134);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-dAsp-NH2(SEQ ID NO: 135);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 142);Ac-Lys-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 144);Ac-His-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 147);Ac-Ala-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 156);Ac-dAla-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 157);Ac-Arg-c[Asp-His-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 158);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAsp-dVal-dPro-NH2(SEQ ID NO: 164);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 165);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 166);Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-dAla-dAla-dAsp-dVal-dPro-NH2(SEQ ID NO: 167); andAc-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-Gly-Gly-dAsp-dVal-dPro-NH2(SEQ ID NO: 168), wherein c represents cyclization through a lactam bond.

36. The pharmaceutical composition of any one of claims 1 -29, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (IB):X1- R1- R2- R3- R4- R5- R6- R7-Y1- Y2- Y3(IB), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);-262-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);R3is selected from the group consisting of His, dHis, phenylalanine (Phe), proline (Pro), biphenylalanine (Bip), glutamine (Gin), and D-glutamine (dGIn);R4is para-fluoro-D-phenylalanine (p(F)dPhe);R5is Arg or His;R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of, Lys, Orn, Cys, and dCys,Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is dVal or dPro;Y3is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys, or Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys; provided that: when R3is His, then (i) R7is Cys or dCys, or (ii) R7is Lys and (a) R6is dNal(2’) or Nal(2’), (b) R1is Ala, or (c) R1is dArg and Y1is dVal, and when R3is Pro, then R2is not Cys, R6is Trp, and the C-terminus is amidated.

37. The pharmaceutical composition of any one of claims 1 -29 and 36, wherein the non-naturally occurring melanocortin analog comprises a sequence of Formula (IB), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, alanine (Ala), arginine (Arg), D- arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);R2is selected from the group consisting of aspartic acid (Asp), cysteine (Cys), and D-cysteine (dCys);-263-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR3is selected from the group consisting of His, dHis, phenylalanine (Phe), proline (Pro), biphenylalanine (Bip), glutamine (Gin), and D-glutamine (dGIn);R4is para-fluoro-D-phenylalanine (p(F)dPhe);R5is Arg or His;R6is selected from the group consisting of Trp, 2’-naphthylalanine (Nal(2’)), and 2’- D-naphthylalanine (dNal(2’));R7is selected from the group consisting of, Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is dVal or dPro;Y3is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys, or Orn; a disulfide bond between R2and R7, when R2and R7are each Cys; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 53);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 54);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 55);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 56);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 57);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 58);Ac-Nle-c[Asp-His-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 59);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 62);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 63);Ac-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 64);-264-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 65);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 66);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 67);Ac-Lys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 68);Ac-dLys-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 69);Ac-His-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 70);Ac-dHis-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 71 );Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 72);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 73);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 87);Ac-Arg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 88);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 91 );Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 92);Ac-Nle-c[Cys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 93);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 96); andAc-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 97), wherein c represents cyclization through a lactam or disulfide bond.

38. The pharmaceutical composition of any one of claims 1 -27, wherein the non- naturally occurring melanocortin analog comprises a sequence of Formula (IC):X1- R1- R2- R3- R4- R5- R6- R7- Y1-Y2-Y3- Y4( I C) , wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);-265-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), glutamic acid (Glu), and D-cysteine (dCys);R3is selected from the group consisting of His, 4-amino-1 ,2,4,5-tetrahydro-2- benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)- one (Ata), and 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia);R4is para-chloro-D-phenylalanine (p(CI)dPhe);R5is Arg;R6is Trp;R7is selected from the group consisting of Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is selected from the group consisting of dVal, dPro, and dTle;Y3is absent, dVal, or dPro;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that: when R1is dArg, then Y1is dTle, and when R1is Nle, R2is Asp, R3is His, and Y2is dPro, then either (i) R7is Orn or (ii) X1is Nle and Y1is dTle.

39. The pharmaceutical composition of any one of claims 1 -27 and 38, wherein the non-naturally occurring melanocortin analog comprises a sequence of Formula (IC), wherein:X1is absent or norlecuine (Nle);R1is selected from the group consisting of Nle, arginine (Arg), D-arginine (dArg), lysine (Lys), D-lysine (dLys), histidine (His), and D-histidine (dHis);-266-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOR2is selected from the group consisting of aspartic acid (Asp), glutamic acid (Glu), and D-cysteine (dCys);R3is selected from the group consisting of His, 4-amino-1 ,2,4,5-tetrahydro-2- benzazepin-3-one (Aba), 7-amino-7,8-dihydro-4H-[1 ,2,3]triazolo-[1 ,5-a][1 ,4]diazepin-6(5H)- one (Ata), and 4-amino-1 ,4,5,6-tetrahydroazepino[4,3-b]indol-3(2H)-one (Aia);R4is para-chloro-D-phenylalanine (p(CI)dPhe);R5is Arg;R6is Trp;R7is selected from the group consisting of Lys, Orn, Cys, and dCys;Y1is selected from the group consisting of D-valine (dVal), D-proline (dPro), and D- tertleucine (dTle);Y2is selected from the group consisting of dVal, dPro, and dTle;Y3is absent, dVal, or dPro;Y4is absent or dPro; and the non-naturally occurring melanocortin analog is cyclized via a moiety selected from the group consisting of: a lactam bond between R2and R7, when R2is Asp and R7is Lys or Orn; a lactam bond between R2and R7, when R2is Glu and R7is Orn; and a disulfide bond between R2and R7, when R2is dCys and R7is Cys or dCys, provided that the non-naturally occurring melanocortin analog does not comprise a sequence selected from the group consisting of:Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 44);Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 45);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 46); andAc-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 47), wherein c represents cyclization through a lactam or disulfide bond.

40. The pharmaceutical composition of any one of claims 1 -39, wherein R4is Phe.-267-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO41. The pharmaceutical composition of any one of claims 1 -40, wherein the sequence of any one of Formulae (l)-(IC) is: Ac-Nle-c[Asp-Pro-Phe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 169); or Ac-Nle-c[Asp-Pro-His-Phe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 170), wherein c represents cyclization through R2and R7via a lactam bond.

42. The pharmaceutical composition of any one of claims 1 -39, wherein R4is dPhe or p(F)dPhe.

43. The pharmaceutical composition of any one of claims 1 -39 and 42, wherein R1is Nle, R3is Pro, R5is Arg, R6is Trp.

44. The pharmaceutical composition of any one of claims 1 -39, 42, and 43, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-OH (SEQ ID NO: 171 );Ac-Nle-c[Glu-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 172);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 3);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Orn]-dVal-dPro-NH2 (SEQ ID NO: 174);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 175);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 176);Ac-Nle-c[dCys-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 296);Ac-Nle-c[dPen-Pro-dPhe-Arg-Trp-dPen]-dVal-dPro-NH2 (SEQ ID NO: 297);Ac-Nle-c[dCys-Pro-dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 298);Ac-Nle-c[dCys-Pro-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2 (SEQ ID NO: 299); andAc-Nle-c[dCys-Pro-p(F)dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 300), wherein c represents cyclization through R2and R7via a lactam bond or a disulfide bond.-268-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO45. The pharmaceutical composition of any one of claims 1 -39, wherein R1is an amino acid other than Nle.

46. The pharmaceutical composition of any one of claims 1 -39 and 45, wherein R1is selected from dLeu, dAla, Ala, dArg, Arg, dTyr, dLys, Lys, dHis, His, dOrn, Orn, Phe, dPhe, Trp, and dTrp.

47. The pharmaceutical composition of any one of claims 1 -39, 45, and 46, wherein Y1is dVal or dTle and Y2is dPro.

48. The pharmaceutical composition of any one of claims 1 -39 and 45-47, wherein R4is dPhe.

49. The pharmaceutical composition of any one of claims 1 -39 and 45-48, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-dLeu-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 177);Ac-dAla-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 178);Ac-Ala-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 179);Ac-dArg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 180);Ac-dTyr-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 181 );Phe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 182);His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 183);Trp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 184); dPhe-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 185); dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 186); dTrp-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 187);-269-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 188);Ac-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 189);Ac-Lys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 190);Ac-His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 191 );Ac-dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 192);Ac-Orn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 193); Ac-dOrn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 194);Ac-Ala-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 195);Ac-dArg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 196);Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 197);Ac-Lys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 198);Ac-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 199);Ac-His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 200);Ac-dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 201 ); andAc-Orn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 202), wherein c represents cyclization through R2and R7via a lactam bond.

50. The pharmaceutical composition of any one of claims 1 -39 and 45-47, wherein R4is p(F)dPhe.

51. The pharmaceutical composition of any one of claims 1 -39, 45-47, and 50, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Ala-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 208);Ac-dArg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 209);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 210);-270-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Lys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 211 );Ac-dLys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 212);Ac-His-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 213);Ac-dHis-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 214);Ac-Ala-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 215);Ac-dArg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 216);Ac-Arg-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 217);Ac-Lys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 218);Ac-dLys-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 219);Ac-His-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 220);Ac-dHis-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 221 );Ac-Ala-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 222);Ac-Ala-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 224);Ac-dArg-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 223); andAc-Ala-c[Asp-His-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 224), wherein c represents cyclization through R2and R7via a lactam bond.

52. The pharmaceutical composition of any one of claims 1 -39 and 45-47, wherein R4is p(CI)dPhe.

53. The pharmaceutical composition of any one of claims 1 -39, 45-47, and 52, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Arg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 225);Ac-Lys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 226);Ac-dLys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 227);-271 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-His-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 228);Ac-dHis-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 229);Ac-dArg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 230);Ac-Arg-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 231 );Ac-Lys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 232);Ac-dLys-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 233);Ac-His-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 234); and Ac-dHis-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 235), wherein c represents cyclization through R2and R7via a lactam bond.

54. The pharmaceutical composition of any one of claims 1 -39, 45, and 46, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Arg-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dVal-dPro-NH2(SEQ ID NO: 203);Ac-dLys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2(03; SEQ ID NO: 4);Ac-Lys-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dPro-NH2(SEQ ID NO: 204);Ac-His-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 205);Ac-dHis-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 206); and Ac-dOrn-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 207), wherein c represents cyclization through R2and R7via a lactam bond.

55. The pharmaceutical composition of any one of claims 1 -39, wherein R3is an amino acid other than Pro or His.-272-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO56. The pharmaceutical composition of any one of claims 1 -39 and 55, wherein R3is selected from Ala, Leu, Hyp, Phe, dPhe, Bip, dGIn, Gin, dHis, Trp, dTrp, loc, Tic, Aba, Aia, Ata, Ate, APC, or APPC.

57. The pharmaceutical composition of any one of claims 1 -39, 55, and 56, wherein R4is dPhe.

58. The pharmaceutical composition of any one of claims 1 -39 and 55-57, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of: the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-loc-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 236);Ac-Nle-c[Asp-Aba-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 237);Ac-Nle-c[Asp-Aia-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 238);Ac-Nle-c[Asp-Ata-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 239);Ac-Nle-c[Asp-APC-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 240);Ac-Nle-c[Asp-APPC-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 241 );Ac-Nle-c[Asp-Ala-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 242);Ac-Nle-c[Asp-Hyp-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 243);Ac-Nle-c[Asp-dPhe-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 244);Ac-Nle-c[Asp-dGln-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 245);Ac-Nle-c[Asp-Trp-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 246);Ac-Nle-c[Asp-dTrp-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 247);Ac-Nle-c[Asp-Tyr-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 248);Ac-Nle-c[Asp-dTyr-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 249);Ac-Nle-c[Asp-Atc-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 250);Ac-Nle-c[Asp-Leu-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 251 );-273-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Tic-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 252);Ac-Nle-c[Asp-Phe-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 253); andAc-Nle-c[Asp-Bip-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 254), wherein c represents cyclization through R2and R7via a lactam bond.

59. The pharmaceutical composition of any one of claims 1 -39, 55, and 56, wherein R4is p(F)dPhe.

60. The pharmaceutical composition of any one of claims 1 -39, 55, 56, and 59, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Gln-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 255);Ac-Nle-c[Asp-dGln-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 256);Ac-Nle-c[Asp-dHis-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 257);Ac-Nle-c[Asp-Phe-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 258); andAc-Nle-c[Asp-Bip-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 259), wherein c represents cyclization through R2and R7via a lactam bond.

61. The pharmaceutical composition of any one of claims 1 -39, 55, and 56, wherein R4is p(CI)dPhe.

62. The pharmaceutical composition of any one of claims 1 -39, 55, 56, and 61 , wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Aba-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 260);Ac-Nle-c[Asp-Aia-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 261 ); andAc-Nle-c[Asp-Ata-p(CI)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 262),-274-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO wherein c represents cyclization through R2and R7via a lactam bond.

63. The pharmaceutical composition of any one of claims 1 -39 and 55, wherein R3is a dipeptide comprising His.

64. The pharmaceutical composition of any one of claims 1 -39, 55, and 63, wherein R3is Ala-His, Phe-His, or Pro-His.

65. The pharmaceutical composition of any one of claims 1 -39, 55, 63, and 64, wherein R4is dPhe.

66. The pharmaceutical composition of any one of claims 1 -39, 55, and 63-65, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Ala-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 263);Ac-Arg-c[Asp-Ala-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 264);Ac-dArg-c[Asp-Ala-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 265);Ac-Nle-c[Asp-Pro-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 266);Ac-Nle-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 267);Ac-Nle-Phe-Phe-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 268);Ac-Nle-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dLeu-dPro-NH2 (SEQ ID NO: 269); andAc-Nle-c[Asp-Phe-His-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 270), wherein c represents cyclization through R2and R7via a lactam bond.

67. The pharmaceutical composition of any one of claims 1 -39 and 55, wherein R3is a dipeptide comprising Pro or a derivative thereof.-275-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO68. The pharmaceutical composition of any one of claims 1 -39, 55, and 67, wherein R3is Trp-Pro or a derivative thereof.

69. The pharmaceutical composition of any one of claims 1 -39, 55, 67, and 68, wherein R4is dPhe.

70. The pharmaceutical composition of any one of claims 1 -39, 55, and 67-69, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 271 );Ac-Nle-c[Cys-Trp-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 272);Ac-Nle-c[dCys-Trp-Pro-dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 273);Ac-Ala-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 274);Ac-Lys-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 275);Ac-dLys-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 276);Ac-Arg-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 277);Ac-dArg-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 278);Ac-dHis-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 279);Ac-His-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 280);Ac-Nle-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 281 );Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dArg-dVal-dPro-NH2(SEQ ID NO: 282);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2(SEQ ID NO: 283);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dArg-dPro-NH2(SEQ ID NO: 284);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dLys-dPro-NH2(SEQ ID NO: 285);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 286);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 287);-276-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Trp-Pro-dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2 (SEQ ID NO: 288);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 289);Ac-Nle-c[Asp-Trp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 290);Ac-Nle-c[Asp-Trp-Ala-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 291 );Ac-Nle-c[Asp-Trp-Leu-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 292);Ac-Nle-c[Asp-Tyr-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 293);Ac-Nle-c[Asp-dPhe-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 294); and Ac-Nle-c[Asp-dTyr-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 295), wherein c represents cyclization through R2and R7via a lactam bond.71 . The pharmaceutical composition of any one of claims 1 -39, wherein R3is Pro.

72. The pharmaceutical composition of any one of claims 1 -39 and 71 , wherein R5is not Arg, R6is not Trp, or R7is not Lys.

73. The pharmaceutical composition of any one of claims 1 -39, 71 , and 72, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Gly-Lys]-dVal-dPro-NH2(SEQ ID NO: 301 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Gly-Lys]-dPro-dPro-Lys-Asp-NH2 (SEQ ID NO: 302);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Gly-Lys]-dPro-dPro-dLys-dAsp-NH2 (SEQ ID NO: 303);Ac-Nle-c[Asp-Pro-dPhe-Lys-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 304);Ac-Nle-c[Asp-Pro-dPhe-transPro(guan)-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 305);Ac-Nle-c[Asp-Pro-dPhe-cisPro(guan)-Trp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 306);Ac-Nle-c[Asp-Pro-p(F)dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 307);Ac-Nle-c[Asp-Pro-dPhe-His-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 308);-277-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-dTrp-Lys]-dVal-dPro-NH2 (SEQ ID NO: 309);Ac-Nle-c[Asp-Pro-dPhe-Arg-Nal(1 ')-Lys]-dVal-dPro-NH2(SEQ ID NO: 310);Ac-Nle-c[Asp-Pro-dPhe-Arg-Phe-Lys]-dVal-dPro-NH2(SEQ ID NO: 311 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 312);Ac-Nle-c[Asp-Pro-dPhe-Arg-Aia-Lys]-dVal-dPro-NH2 (SEQ ID NO: 313);Ac-Nle-c[Asp-Pro-dPhe-Arg-Aba-Lys]-dVal-dPro-NH2 (SEQ ID NO: 314); andAc-Nle-c[Asp-Pro-dPhe-Arg-Ata-Lys]-dVal-dPro-NH2 (SEQ ID NO: 315), wherein c represents cyclization through R2and R7or R8via a lactam bond.

74. The pharmaceutical composition of any one of claims 1 -39 and 71 , wherein the N-terminus is extended and / or the C-terminus is not dVal-dPro.

75. The pharmaceutical composition of any one of claims 1 -39, 71 , and 74, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Val-Pro-NH2 (SEQ ID NO: 316);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-Hyp-NH2(SEQ ID NO: 317);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dHyp-NH2(SEQ ID NO: 318);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Val-NH2(SEQ ID NO: 319);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Pro-NH2 (SEQ ID NO: 320);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dArg-NH2(SEQ ID NO: 321 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dPro-NH2 (SEQ ID NO: 322);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-NH2 (SEQ ID NO: 323);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-NH2 (SEQ ID NO: 324);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-Pro-Val-NH2 (SEQ ID NO: 325);-278-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-dVal-dPro-NH2 (SEQ ID NO: 326);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dLys-dVal-dPro-NH2 (SEQ ID NO: 327);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-Pro-Val-NH2 (SEQ ID NO: 328);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Arg-Val-Pro-NH2 (SEQ ID NO: 329);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dArg-dVal-dPro-NH2 (SEQ ID NO: 330);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 331 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dTle-dPro-NH2(SEQ ID NO: 332);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 333);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dTle-NH2(SEQ ID NO: 334);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dPro-NH2(SEQ ID NO: 335);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2 (SEQ ID NO: 336);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 337);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-dVal-dPro-NH2(SEQ ID NO: 338);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 339);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Trp-NH2 (SEQ ID NO: 340);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-dPro-dVal-NH2 (SEQ ID NO: 341 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAla-dAla-NH2 (SEQ ID NO: 342);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dHyp-NH2 (SEQ ID NO: 343);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dAsn-NH2 (SEQ ID NO: 344);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-Asp-NH2 (SEQ ID NO: 345);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asn-dPro-NH2 (SEQ ID NO: 346);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Hyp-NH2 (SEQ ID NO: 347);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Ala-Ala-NH2 (SEQ ID NO: 348);-279-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Gly-Gly-NH2 (SEQ ID NO: 349);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asp-dPro-NH2 (SEQ ID NO: 350);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsn-dPro-NH2 (SEQ ID NO: 351 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Asn-NH2 (SEQ ID NO: 352);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsp-NH2 (SEQ ID NO: 353);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dAsn-NH2 (SEQ ID NO: 354);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-Lys-dPro-NH2 (SEQ ID NO: 355);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-OH (SEQ ID NO: 356);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dThr-dPro-dThr-OH (SEQ ID NO: 357);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-NH2 (SEQ ID NO: 358);Ac-Nle-c[dAsp-Pro-dPhe-Arg-Trp-dLys]-dPro-dVal-NH2(SEQ ID NO: 359);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-pPro-p2Val-NH2 (SEQ ID NO: 360);Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-pPro-p3Val-NH2 (SEQ ID NO: 361 );Ac-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-pPro-pPro-NH2 (SEQ ID NO: 362);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2 (SEQ ID NO: 363);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2 (SEQ ID NO: 364);Ac-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 365);Ac-Nle-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 366);Ac-Nle-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 367);Ac-Nle-Nle-c[Asp-Pro-p(F)dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 368);Ac-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dTle-dPro-NH2 (SEQ ID NO: 369); and Ac-Nle-Nle-Nle-Nle-c[Asp-Pro-dPhe-Arg-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 370), wherein c represents cyclization through R2and R7via a lactam bond.-280-SMRH:4930-9487-9852.5Docket No.: 183B-412978-WO76. The pharmaceutical composition of any one of claims 1 -39, wherein R3is His.

77. The pharmaceutical composition of any one of claims 1 -39 and 76, wherein R1is Nle, R4is p(CI)dPhe or p(F)dPhe, R5is Arg, and R6is Trp.

78. The pharmaceutical composition of any one of claims 1 -39, 76, and 77, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 371 );Ac-Nle-c[Glu-His-p(CI)dPhe-Arg-Trp-Orn]-dVal-dPro-NH2(SEQ ID NO: 372);Ac-Nle-c[dCys-His-p(CI)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 373);Ac-Nle-c[dCys-His-p(CI)dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 374);Ac-Nle-c[Cys-His-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 375);Ac-Nle-c[dCys-His-p(F)dPhe-Arg-Trp-Cys]-dVal-dPro-NH2(SEQ ID NO: 376); andAc-Nle-c[dCys-His-p(F)dPhe-Arg-Trp-dCys]-dVal-dPro-NH2(SEQ ID NO: 377), wherein c represents cyclization through R2and R7via a lactam bond or a disulfide bond.

79. The pharmaceutical composition of any one of claims 1 -39 and 76, wherein R5is not Arg, R6is not Trp, or R7is not Lys.

80. The pharmaceutical composition of any one of claims 1 -39, 76, and 79, wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Pro-Lys]-dVal-dPro-NH2(SEQ ID NO: 378);Ac-Nle-c[Asp-His-dPhe-transPro(guan)-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 379);Ac-Nle-c[Asp-His-dPhe-cisPro(guan)-Trp-Lys]-dVal-dPro-NH2(SEQ ID NO: 380);Ac-Nle-c[Asp-His-p(F)dPhe-Arg-dNal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 381 ); and-281 -SMRH:4930-9487-9852.5Docket No.: 183B-412978-WOAc-Nle-c[Asp-His-p(F)dPhe-Arg-Nal(2')-Lys]-dVal-dPro-NH2(SEQ ID NO: 390), wherein c represents cyclization through R2and R7via a lactam bond.

81. The pharmaceutical composition of any one of claims 1 -39 and 76, wherein the N-terminus is extended and / or the C-terminus is not dVal-dPro.

82. The pharmaceutical composition of any one of claims 1 -39, 76, and 81 , wherein the sequence of any one of Formulae (l)-(IC) is selected from the group consisting of:Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 382)Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dTle-dVal-NH2(SEQ ID NO: 383);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dVal-dVal-dVal-dPro-NH2(SEQ ID NO: 384);Ac-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dPro-dVal-dPro-NH2(SEQ ID NO: 385); and Ac-Nle-Nle-c[Asp-His-p(CI)dPhe-Arg-Trp-Lys]-dTle-dPro-NH2(SEQ ID NO: 386), wherein c represents cyclization through R2and R7via a lactam bond.-282-SMRH:4930-9487-9852.5

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