Combinations of a potassium channel activator and an mc4r agonist and related methods of use

Abstract

The disclosure relates to a method of treating a disease or disorder in a subject using a combination of: (i) a potassium channel activator (e.g., a SURx / Kirx channel activator compound) or a pharmaceutically acceptable salt thereof; and (ii) a melanocortin-4 receptor (MC4R) agonist.

Description

[0001] Attorney Docket No.: R2054-7034WO COMBINATIONS OF A POTASSIUM CHANNEL ACTIVATOR AND AN MC4R AGONIST AND RELATED METHODS OF USE CLAIM OF PRIORITY The present application claims priority to U.S. Application No.63 / 548,506, filed on November 14, 2023, the entire contents of which is hereby incorporated by reference. BACKGROUND The melanocortin 4 receptor (MC4R) is a heterotrimeric G-protein-coupled receptor that transduces signals by activating adenylate cyclase. MC4R is primarily expressed in neuronal tissue and plays a role in controlling feeding behavior and energy homeostasis by, for example, integrating an agonist signal provided by the α-melanocyte stimulating hormone (α-MSH), and an antagonist signal provided by the agouti-related peptide (AGRP). MC4R is a part of the leptin-melanocortin pathway, also known as the POMC-MC4R pathway, which includes a number of proteins such as leptin, leptin receptors, pro-opiomelanocortin (POMC), and prohormone convertases including PCSK1, α-MSH, and others. In mammals, the hypothalamic POMC-MC4R pathway is part of the regulatory network of appetite and body. While agonism of the MC4R pathway has shown to be an effective treatment for weight loss in certain contexts, there is a desire for enhancement of this treatment and thus interest in exploring certain combination therapies. SUMMARY The present disclosure features methods of treating and / or preventing a disease or disorder in a subject comprising administering a combination of a potassium channel activator (e.g., SURx / Kirx channel activator compound, e.g., a SUR1 / Kir6.1 or SUR1 / Kir6.2 channel activator compound), or a pharmaceutically acceptable salt thereof and an MC4R agonist, or a pharmaceutically acceptable salt thereof, to the subject. In an embodiment, the SURx / Kirx channel activator compound is a compound having the structure of Formula (XIV), or a pharmaceutically acceptable salt thereof, e.g., as described herein. In an embodiment, the MC4R agonist is a peptide or a small molecule. In an embodiment, the MC4R agonist is a small molecule, e.g., a peptidomimetic small molecule. In an embodiment, the MC4R agonist is a Attorney Docket No.: R2054-7034WO peptide. In an embodiment, the MC4R agonist is selected from a structure of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII) or a pharmaceutically acceptable salt thereof, e.g., as described herein. In one aspect, the method comprises administering the combination such that the SURx / Kirx channel activator compound is between about 1 mg / kg to about 200 mg / kg, and the dosage of the MC4R agonist is between about 0.5 mg / kg to about 20 mg / kg. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered as a single formulation. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered as a separate formulations. In an embodiment, the SURx / Kirx channel activator compound is formulated for oral administration. In an embodiment, the SURx / Kirx channel activator compound is formulated for parenteral administration. In an embodiment, the SURx / Kirx channel activator compound is formulated for subcutaneous administration. In an embodiment, the MC4R agonist is formulated for parenteral administration. In an embodiment, the MC4R agonist is formulated for subcutaneous administration. In an embodiment, the MC4R agonist is formulated for oral administration. In an embodiment, the ratio of the amount of the SURx / Kirx channel activator compound to the MC4R agonist in the combination is between 200:1 to 1:1. In another aspect, the method comprises treating and / or preventing a disease or disorder, e.g., obesity or an obesity-related disorder, such as hyperphagia or hypothalamic obesity, with a combination of a potassium channel activator (e.g., SURx / Kirx channel activator compound, e.g., a SUR1 / Kir6.1 or SUR1 / Kir6.2 channel activator compound), or a pharmaceutically acceptable salt thereof and an MC4R agonist, or a pharmaceutically acceptable salt thereof . In an embodiment, the disease or disorder is a metabolic syndrome. In some embodiments, the metabolic disorder is a genetic or epigenetic disorder, e.g., Prader-Willi syndrome, Alström syndrome, Bardet-Biedl syndrome, or Smith-Magenis syndrome. In an embodiment, the disease or disorder is Prader Willi syndrome or congenital hyperinsulinism (CHI). In an embodiment, the disease or disorder is a behavioural disorder or a psychological disorder. In an embodiment, the disease or disorder is obesity (e.g., a genetic obesity or a non-genetic obesity, e.g., an acquired obesity). Attorney Docket No.: R2054-7034WO The present disclosure further contemplates compositions, e.g., pharmaceutical compositions, as well related methods of making. Further embodiments of the present disclosure are provided herein in the Description, Drawings, Examples, and Claims. BRIEF DESCRIPTION OF THE DRAWINGS FIGS.1A-B demonstrate the synergistic effects of an exemplary MC4R agonist (MC4R Agonist I) and an exemplary SURx / Kirx channel activator compound I (SURx / Kirx channel activator compound I) on body weight in obese Zucker rats over a 21-day period. FIG.1A is a plot of the body weight (grams) of Zucker rats administered placebo (5 mg / kg), SURx / Kirx channel activator compound I (150, 50, 80 and 100 mg / kg / day from day 1-6, 7-13, 13-17, 17-22 respectively), and SURx / Kirx channel activator compound I (150, 50, 80 and 100 mg / kg / day from day 1-6, 7-13, 13-17, 17-22 respectively) + MC4R Agonist I (5 mg / kg / week) over 21 days. FIG.1B is a plot of the body weight of Zucker rats administered placebo depot injection (5 mg / kg, subcutaneous (SC), once per week), a second exemplary MC4R agonist (MC4R Agonist II) depot injection (30 mg / mL, 5 mg / kg, SC, once per week), MC4R Agonist I depot injection (30 mg / mL, 5 mg / .kg, SC, once per week) and MC4R Agonist I depot injection (30 mg / mL, 10 mg / kg, SC, once per week). FIGS.2A-B are graphs of the cumulative food intake of Zucker rats administered placebo, SURx / Kirx channel activator compound I alone, or a combination of SURx / Kirx channel activator compound + MC4R agonist compound. FIG.2A is a graph of the cumulative food intake of Zucker rats over the 21-day period administered placebo, SURx / Kirx channel activator compound I (150, 50, 80 and 100 mg / kg / day from day 1-6, 7-13, 13-17, 17-22 respectively) and SURx / Kirx channel activator compound I (150, 50, 80 and 100 mg / kg / day from day 1-6, 7-13, 13-17, 17-22 respectively) + MC4R Agonist I (5 mg / kg / weekly) in the Experiment 1 study. FIG 2B is a plot of the cumulative food intake (g) of male Zucker rats over the 21 days in all 3 groups of male Zucker rats in Experiment 2 over 21 days that were treated with placebo (5 mg / kg), SURx / Kirx channel activator compound I (50, 80 and 100 mg / kg / day from day 1-6, 6-10, 10-21 respectively) and SURx / Kirx channel activator compound I (50, 80 and 100 mg / kg / day from day 1-6, 6-10, 10-21 respectively) + MC4R Agonist I (5 mg / kg / week). FIGS.3A-C are plots of the plasma glucose, insulin, and leptin in obese Zucker rats in the fed state in the Experiment 1 over 17 days. Zucker rats were administered placebo, Attorney Docket No.: R2054-7034WO SURx / Kirx channel activator compound I and SURx / Kirx channel activator compound I + MC4R Activator Is (5mg / kg / week). FIG 3A is a plot of the plasma glucose concentration (mM) in the Zucker rats during Experiment 1. FIG.3B is a plot of the plasma insulin concentration(ng / mL) in the Zucker rats during the experiment. FIG 3C is a plot of the plasma leptin concentration (ng / mL) in the Zucker rats during the experiment. FIGS.4A-B show the results of the oral glucose tolerance test (2g / kg glucose given after overnight fast) at the end of the 21-day in Experiment 1 in Zucker rats administered placebo, SURx / Kirx channel activator compound I (100 mg / kg / day), and SURx / Kirx channel activator compound I (100mg / kg / day) + MC4R Agonist I (5 mg / kg / week). FIG.4A is a plot of the plasma glucose concentration (mg / dL) in the Zucker rats over 120 min. FIG.4B is a plot of the plasma insulin (ng / mL) concentration over 120 min. FIG.5 is a graph of the body weight changes of male Zucker rats in the Experiment 2 during 21-day administration of placebo (5 mg / kg), SURx / Kirx channel activator compound I 50, 80 and 100 mg / kg / day from day (1-6, 6-10, 10-21 respectively) and SURx / Kirx channel activator compound I (50, 80 and 100 mg / kg / day from day 1-6, 6-10, 10-21 respectively) + MC4R Agonist I (5 mg / kg / week). FIG.6 is a bar graph of the weekly body weight gain for the male obese Zucker rats for Days 1-7, Days 7-14, Days 14-20, and overall from Days 1-20. FIGS.7A-7B are plots of the plasma glucose and insulin in fed Zucker rats in Experiment 2. FIG.7A shows plasma glucose concentration (mM) in the Zucker rats over the course of Experiment 2. FIG.7B is a graph of plasma insulin concentration (ng / mL) in the Zucker rats through Experiment 2. All data presents mean (sem). FIGS.8A-8D show the results of the oral glucose tolerance test (2g / kg glucose given after overnight fast) for the both the combined and main study in Zucker rats administered placebo (5 mg / kg), SURx / Kirx channel activator compound I (100 mg / kg / day) and SURx / Kirx channel activator compound I (100mg / kg / day) + MC4R Agonist I (5 mg / kg). FIG.8A is a plot of the plasma glucose concentration (mg / dL) in the Zucker rats over the course of 120 min. FIG. 8B is a bar graph showing the plasma glucose (mg / dL) for the Placebo, SURx / Kirx Channel Activator I, and SURx / Kirx Channel Activator I + MC4R Agonist I groups for the combined pilot and main study. FIG.8C is a plot of the plasma insulin concentration (ng / mL) in the Zucker rats over for 120 min. FIG.8D is a bar graph showing the plasma insulin (ng / mL) for the Attorney Docket No.: R2054-7034WO Placebo, SURx / Kirx Channel Activator I, and SURx / Kirx Channel Activator I + MC4R Agonist I groups for the combined pilot and main study. FIGS.9A-9D show the calculated areas under the curve (AUC) for plasma insulin and glucose for the OGTT measurements in FIGS.8A-D. Shown is the mean (SEM) n=4. FIG.9A are plots of the glucose AUC (0-60 min) and glucose (0-120 min) for the treatment groups: placebo, SURx / Kirx channel activator compound I (100 mg / kg) and SURx / Kirx channel activator compound I (100mg / kg)+ MC4R Agonist I (5 mg / kg). FIG.9B is a bar graph of the glucose AUC (0-60 min) for the Placebo, SURx / Kirx Channel Activator I, and SURx / Kirx Channel Activator I + MC4R Agonist I groups for the combined pilot and main study. FIG.9C are plots of the insulin AUC (0-60 min) and insulin AUC (0-120 min) for the three treatment groups: placebo, SURx / Kirx channel activator compound I (100 mg / kg) and SURx / Kirx channel activator compound I (100mg / kg)+ MC4R Agonist I (5 mg / kg / week). All data present means (sem). FIG.9D is a bar graph of the insulin AUC (0-60 min) for the Placebo, SURx / Kirx Channel Activator I, and SURx / Kirx Channel Activator I + MC4R Agonist I groups for the combined pilot and main study. FIGS.10A-10D are bar graphs of plasma fat and inflammatory hepatic biomarkers in samples collected on day 17 (fed state) in Experiment 2. All data presents mean (sem). FIG. 10A-B are bar graphs of plasma cholesterol concentration (mg / dL) and total triglycerides (mmol / L) for placebo, SURx / Kirx channel activator compound I (100 mg / kg / day) and SURx / Kirx channel activator compound I (100 mg / kg / day) + MC4R Agonist I (5 mg / kg / week). FIG.10C is a bar graph of plasma aspartate aminotransferase (AST, U / L) for placebo, SURx / Kirx channel activator compound I (100 mg / kg / day) and SURx / Kirx channel activator compound I(100 mg / kg / day) + MC4R Agonist I (5 mg / kg / week). FIG.10D is a bar graphs for plasma alanine transaminase (ALT, U / L) for placebo, channel activator compound I (100 mg / kg / day) and SURx / Kirx channel activator compound I(100 mg / kg / day) + MC4R Agonist I (5 mg / kg / week). FIGS.11A-11D are bar graphs of hepatic parameters, i.e., liver cholesterol (mg / g), liver triglycerides (mg / g), liver nonesterified fatty acids (NEFA, mg / g) and liver glycogen (µg / g) for placebo, SURx / Kirx channel activator compound I (100 mg / kg / day) and SURx / Kirx channel activator compound I(100 mg / kg / day) + MC4R Agonist I (5 mg / kg / week) in Experiment 2. Attorney Docket No.: R2054-7034WO FIG.12A-B are plots demonstrating the effect of SURx / Kirx channel activator compound I and MC4R Agonist I on body weight reduction over MC4R Agonist I alone or SURx / Kirx channel activator compound I, in which the obese Zucker rats were administered an initially high dose of SURx / Kirx channel activator compound I, which was subsequently reduced. The three treatment groups were SURx / Kirx channel activator compound I (150, 50, 80 and 100 mg / kg / day from day 1-6, 7-13, 13-17, 17-22 respectively), SURx / Kirx channel activator compound I (150, 50, 80 and 100 mg / kg / day from day 1-6, 7-13, 13-17, 17-22 respectively) + MC4R Agonist I (5 mg / kg / week), and MC4R Agonist I (5 mg / kg / week). All data are shown mean (sem), SURx / Kirx channel activator compound I + MC4R Agonist 1 vs MC4R Agonist I: p<0.05 from day 3 up to day 21. FIG.13 is a plot demonstrating the effect of SURx / Kirx channel activator compound I and MC4R Agonist I on body weight reduction compared to MC4R agonist I alone or SURx / Kirx channel activator I alone, in which the obese Zucker rats were administered an initially low dose of SURx / Kirx channel activator compound I, which was subsequently increased as part of Experiment 2. The three treatment groups were SURx / Kirx channel activator compound I (50, 80 and 100 mg / kg / day from day 1-6, 6-10, 10-21 respectively), SURx / Kirx channel activator compound I (50, 80 and 100 mg / kg / day from day 1-6, 6-10, 10-21 respectively) + MC4R Agonist I (5 mg / kg / weekly), and MC4R Agonist I (5 mg / kg / weekly). All data are shown mean (sem), SURx / Kirx channel activator compound I + MC4R Agonist 1 (5 mg / kg / week) vs + MC4R Agonist I (5 mg / kg / week):p<0.05 from day 3 till the end of the study. FIGS.14A-E are plots demonstrating the effect of the once-weekly MC4 agonist I and SURx / Kirx channel activator compound I (100 mg / kg / day) vs SURx / Kirx channel activator compound I (100 mg / kg / day) alone or Placebo on liver histology in obese male Zucker rats in the pilot study, including steatosis, hepatocellular ballooning, lobular inflammation, lipid deposition and total NAS in Experiment 1. FIGS.15A-E are plots demonstrating the effect of the once-weekly MC4 agonist I and SURx / Kirx channel activator compound I (100 mg / kg / day) vs SURx / Kirx channel activator compound I (100 mg / kg / day) alone or Placebo on liver histology in obese male Zucker rats in the pilot study, including steatosis, hepatocellular ballooning, lobular inflammation, lipid deposition and total NAS in Experiment 2. The significant reduction (p<0.05) in measured steatosis, Attorney Docket No.: R2054-7034WO hepatocellular ballooning, lobular inflammation, lipid deposition and total NAS from placebo is shown [mean (sem)]. FIGS.16A-B are graphs showing the percent change in body weight compared to Placebo for the repeat study for various doses of SURx / Kirx Channel Activator I dose regimes, comparing the Placebo, SURx / Kirx Channel Activator I, and SURx / Kirx Channel Activator I + MC4R Agonist I, and MC4R Agonist I (Original). FIGS.17A-B are graphs showing the percent change cumulative food intake compared to Placebo for the repeat study for various doses of SURx / Kirx Channel Activator I dose regimes, comparing the Placebo, SURx / Kirx Channel Activator I, and SURx / Kirx Channel Activator I + MC4R Agonist I, and MC4R Agonist I (Original). FIG.18 is a table showing the SURx / Kirx Channel Activator I and MC4R Agonist concentrations in liver, CSF, and plasma at a dose for the SURx / Kirx Channel Activator I (100 mg / kg / d) + MC4 Activator I ( 5 mg / kg) combo arm. FIGS.19A-D are graphs showing the percentage changes in carcass weight (FIG.19A), fat (FIG.19B), protein (FIG.19C), and water (FIG.19D) for the SURx / Kirx Channel Activator I alone (repeat), SURx / Kirx Channel Activator I + MC4R Agonist I 5 mg / kg (repeat), MC4R Agonist II 5 mg / kg (original), and MC4R Agonist I 5 mg / kg (original) groups. DETAILED DESCRIPTION Described herein are combinations of a potassium channel activator compound (i.e., a SURx / Kirx channel activator compound) and MC4R agonist, as well as compositions thereof and related methods of use. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered to a subject in combination in order to treat and / or prevent a disease, disorder, or condition, for example, an obesity or obesity-related condition. In an embodiment, the subject is diagnosed with obesity or an obesity-related condition. Definitions As used herein “about” and "approximately" generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given value or range of values. Attorney Docket No.: R2054-7034WO “Acquire” or “acquiring” as the terms are used herein, refer to obtaining possession of a physical entity, or a value, e.g., a numerical value, or knowledge of (e.g., knowledge of the sequence or mutational state of) a genotype or a nucleic acid or polypeptide, by “directly acquiring” or “indirectly acquiring” the physical entity, value, or knowledge. “Directly acquiring” means performing a physical process (e.g., performing a synthetic or analytical method) to obtain the physical entity, value, or knowledge. “Indirectly acquiring” refers to receiving the physical entity, value, or knowledge from another party or source (e.g., a third-party laboratory that directly acquired the physical entity, value, or knowledge). Directly acquiring a physical entity includes performing a process that includes a physical change in a physical substance, e.g., a starting material. Exemplary changes include making a physical entity from two or more starting materials, shearing or fragmenting a substance, separating or purifying a substance, combining two or more separate entities into a mixture, performing a chemical reaction that includes breaking or forming a covalent or non-covalent bond. Directly acquiring a value or knowledge includes performing a process that includes a physical change in a sample or another substance. Examples include performing an analytical process which includes a physical change in a substance, e.g., a sample, analyte, or reagent (sometimes referred to herein as “physical analysis”), performing an analytical method, e.g., a method which includes one or more of the following: separating or purifying a substance, e.g., an analyte, or a fragment or other derivative thereof, from another substance; combining an analyte, or fragment or other derivative thereof, with another substance, e.g., a buffer, solvent, or reactant; or changing the structure of an analyte, or a fragment or other derivative thereof, e.g., by breaking or forming a covalent or non-covalent bond, between a first and a second atom of the analyte; or by changing the structure of a reagent, or a fragment or other derivative thereof, e.g., by breaking or forming a covalent or non-covalent bond, between a first and a second atom of the reagent. As used herein, the term “obese” refers to a subject having a body mass index (BMI) within the ranges defined as “obese” by the Center for Disease Control (see, e.g., URL.cdc.gov / obesity / defining.html and www.cdc.gov / obesity / childhood- / defining.html, last accessed on August 26, 2012) or as defined by “Clinical Guidelines on the Attorney Docket No.: R2054-7034WO Identification, Evaluation, and Treatment of Overweight and Obesity in Adults” from the National Institutes of Health. BMI is obtained by dividing a subject’s weight, e.g., in kilograms (kg) by the square of the subject’s height, e.g., in meter (m). For example, an adult who has a BMI of 30 kg / m2or higher is considered obese. For example, an adult with a BMI of 25.0 to 29.9 kg / m2is considered overweight; an adult with a BMI of 18.5 to 24.9 kg / m2is considered to have a normal or healthy weight range; and an adult with a BMI of less than 18.5 kg / m2is considered to be underweight. For example, an adult having a height of 5 feet, 9 inches with a body weight of 203 pounds or more is considered obese. For pediatric subject, e.g., children and teens, obese refers to a subject having a BMI at or above the 85thto 95thpercentile for pediatric subjects, e.g., children and teens, of the same age and sex. As used herein, a “weekly average of daily most hunger score” refers to the average or mean of the daily most score hunger score of a subject for a period of week or seven days. A “severely obese” subject or a subject having “severe obesity” refers to a subject having a BMI of 35 kg / m2or higher, e.g., 40 kg / m2or higher. For example, a severely obese subject is over 100% over the ideal (normal, healthy) body weight. As used herein “early onset”, e.g., as in early onset obesity, refers to an onset (e.g., first occurrence of one or more symptoms of a disorder, e.g., a disorder described herein, e.g., obesity) that occurs in a subject before adulthood, e.g., during childhood, e.g., when the subject is less 18 years of age or younger (e.g., 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 year of age or younger, or during adolescence, e.g., when the child is younger than 12 years of age or when the child is younger than 6 years of age). As used herein, the term “metabolic syndrome” refers to a group of symptoms that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes. In an embodiment, e.g., according to the American Heart Association and the National Heart, Lung, and Blood Institute, metabolic syndrome (also referred to as Syndrome X) is present if a subject has three or more of the following signs: 1) Blood pressure equal to or higher than 130 / 85 mmHg; 2) Fasting blood sugar (glucose) equal to or higher than 100 mg / dL; 3) Large waist circumference (length around the waist): - Men - 40 inches or more; - Women - 35 inches or more; 4) Low HDL cholesterol: - Men - under 40 mg / dL; - Women - under 50 mg / dL; 5) Triglycerides equal to or higher than 150 mg / dL. Metabolic syndrome can be diagnosed by Attorney Docket No.: R2054-7034WO testing subject’s blood pressure, blood glucose level, HDL cholesterol level, LDL cholesterol level, total cholesterol level, and triglyceride level. As used herein, the term “agonist” refers to any chemical compound, either naturally occurring or synthetic, that, upon interacting with (e.g., binding to) its target, e.g., MC4R, raises the signaling activity of MC4R above its basal level. An agonist can be a superagonist (i.e., a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%), a full agonist (i.e. a compound that elicits a maximal response following receptor occupation and activation) or a partial agonist (i.e., a compounds that can activate receptors but are unable to elicit the maximal response of the receptor system). As used herein “treating” includes achieving one or more of the following results: reducing the body weight (as measured, for example, by a body mass index (BMI) and / or body weight), e.g., compared to a control (e.g., body weight before treatment or a predetermined body weight); reducing the waist circumference, e.g., compared to a control (e.g., waist circumference before treatment or a predetermined waist circumference); reducing the hunger level, e.g., compared to a control (e.g., hunger level before treatment or a predetermined hunger level); increasing the resting energy expenditure (REE), e.g., compared to a control (e.g., REE before treatment or a predetermined REE); decreasing the food intake, e.g., compared to a control level (e.g., before treatment or a predetermined food intake); ameliorating or improving a clinical symptom or indicators associated with a disorder described herein such as obesity, Prader Willi Syndrome, Smith-Magenis syndrome, e.g., type-II diabetes, pre-diabetic condition, blood level of hemoglobin A1C (Hb1Ac) above 6%, hyperinsulinemia, hyperlipidemia, insulin insensitivity, or glucose intolerance; delaying, inhibiting or preventing the progression of obesity and / or obesity related indications; or partially or totally delaying, inhibiting or preventing the onset or development of obesity or a obesity related indication. Delaying, inhibiting or preventing the progression of the obesity includes for example, delaying, inhibiting or preventing the progression of a subject having normal weight to obesity. In embodiments, a control is a value of a parameter measured before treatment by a MC4R agonist described herein or a predetermined value. The term “treating” further includes partially or totally reducing the risk for coronary artery disease, stroke, and type 2 diabetes associated with the metabolic syndrome as well as ameliorating or improving a clinical symptom or signs of metabolic syndrome Attorney Docket No.: R2054-7034WO associated with metabolic syndrome, such as any one or more of the five indicators listed above. For example, the term “treating” includes delaying, inhibiting or preventing the progression of parameters associated with the metabolic syndrome, including insulin resistance, glucose clearance and parameters of cardiovascular disease including heart rate and blood pressure. As used herein “inhibition” or “inhibits” can include a reduction in a certain parameter, such as a parameter described herein. For example, inhibition of a parameter, e.g., activity, can be at least 5%, 10%, 20%, 30%, 40%, or more is included by this term. Thus, inhibition need not be 100%. As used herein, the term “prophylactic treatment” refers to treatment before onset of obesity to prevent, inhibit or reduce its occurrence. As used herein, the term “potassium channel activator compound” is a compound that binds to and / or activates (e.g., induces the opening of or prolongs the open state of) a potassium channel. In an embodiment, a potassium channel activator compound hyperpolarizes the cell membrane and / or promotes potassium efflux. In an embodiment, a potassium channel activator compound enhances cell membrane permeability to potassium ions. In an embodiment, a potassium channel activator prevents intracellular penetration of calcium. In an embodiment, the potassium channel activator compound is a SURx or Kirx channel activator compound (e.g., a SURx / Kirx channel activator compound, e.g., a SUR1 / Kir6.2 channel activator compound). Exemplary potassium channel activator compounds include aprikalim, bimakalim, cromakalim, emakalim, levcromakalim, diazoxide, nicorandil, pinacidil, retigabine, minoxidil, and tifenazoxide (NN414), NNC 55-0118, as well as pharmaceutically acceptable salts thereof. As used herein, the term “subject” refers to a mammal, e.g., a human. Subject can also refer to an animal in need of veterinary treatment, e.g., companion animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, sheep, pigs, horses, and the like) and laboratory animals (e.g., rats, mice, guinea pigs, and the like). In an embodiment, the subject is a pediatric subject (e.g., a subject under 21 or 18 years of age). In an embodiment, the subject is an adult subject (e.g., a subject over 18 or 21 years of age). As used herein “unit dosage form” refers to a physically discrete unit suited as unitary doses for a subject to be treated. Each unit contains a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. Attorney Docket No.: R2054-7034WO As used herein “dosage” refers to a quantity or amount of a therapeutic agent. In some embodiments, a dosage is the amount administered to the subject in a single administration, e.g., in a single injection, a single infusion, or single administration of one or more unit dosages. In embodiments, a dosage is the amount administered to the subject in multiple administrations, e.g., multiple injections, multiple infusions, or multiple administrations of one or more unit dosages. In other embodiments, a dosage can refer to the total amount administered to the subject in a certain time period, e.g., per day. In such examples, the dosage is typically referred to as “daily dosage” or dosage in terms of quantity per day. As used herein “hunger” or “hunger level” refers to a subject’s appetite, desire to consume food, or perceived need for food. In an embodiment, hunger comprises an inability to recognize that one is full (satiety), a constant preoccupation with food, persistent food-seeking behaviors, abnormal behaviors (e.g., emotional outbursts or violence), or an inability to concentrate, e.g., in the presence or absence of food. In embodiments, the hunger or hunger level of a subject can be quantified by using a scale to obtain a hunger score. In embodiments, the scale for hunger assigns a higher score for a subject that more frequently (e.g., often or always) feels unbearable hunger and a lower score for a subject that less frequently (e.g., sometimes or never) feels unbearable hunger. See, e.g., Sibilia. Psychological Topics 19 (2010), 2, 341-354. For example, a Likert scale for hunger can be used that assigns scores from 0 to 10 points (0=no hunger; 10=severe hunger). In other examples, a Likert scale for hunger can be used that assigns scores from 1 to 4 points, where a subject who never feels unbearable hunger is assigned a score of 1, where a subject who sometimes feels unbearable hunger is assigned a score of 2, where a subject who often feels unbearable hunger is assigned a score of 3, and where a subject who always feels unbearable hunger is assigned a score of 4. See Id. Selected Chemical Definitions Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of Attorney Docket No.: R2054-7034WO organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March’s Advanced Organic Chemistry, 5thEdition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rdEdition, Cambridge University Press, Cambridge, 1987. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. Also, all publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The nomenclature used to define the peptides is that typically used in the art wherein the amino group at the N-terminus appears to the left and the carboxyl group at the C-terminus appears to the right. Where the amino acid has D and L isomeric forms, it is the L form of the amino acid that is represented unless otherwise explicitly indicated. When a range of values is listed, it is intended to encompass each value and sub–range within the range. For example, “C1-C6alkyl” is intended to encompass, C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4- C5, and C5-C6alkyl. The compounds useful for practicing the methods described herein may possess one or more chiral centers and so exist in a number of stereoisomeric forms. All stereoisomers and mixtures thereof are included in the scope of the present disclosure. Racemic compounds may either be separated using preparative HPLC and a column with a chiral stationary phase or resolved to yield individual enantiomers utilizing methods known to those skilled in the art. In addition, chiral intermediate compounds may be resolved and used to prepare chiral compounds of the disclosure. The compounds useful for practicing the methods described herein may also comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including1H,2H (D or deuterium), and3H (T or tritium); C may be in any isotopic form, including12C,13C, and14C; O may be in any isotopic form, including16O and18O; and the like. Attorney Docket No.: R2054-7034WO The term "pharmaceutically acceptable salt" as used herein is meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds used in the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds used in the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galacturonic acids and the like (see, e.g., Berge et al, Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds used in the present disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. These salts may be prepared by methods known to those skilled in the art. Other pharmaceutically acceptable carriers known to those of skill in the art are suitable for use in the present disclosure. The compounds useful for practicing the methods described herein can also exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present disclosure. The compounds useful for practicing the methods described herein may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present disclosure and are intended to be within the scope of the present disclosure. Attorney Docket No.: R2054-7034WO The term “solvate” refers to forms of the compound that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds described herein may be prepared, e.g., in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric solvates and non-stoichiometric solvates. The term “hydrate” refers to a compound which is associated with water. Typically, the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R⋅x H2O, wherein R is the compound and wherein x is a number greater than 0. The term “tautomer” as used herein refers to compounds that are interchangeable forms of a compound structure, and that vary in the displacement of hydrogen atoms and electrons. Thus, two structures may be in equilibrium through the movement of π electrons and an atom (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. Tautomeric forms may be relevant to the attainment of the optimal chemical reactivity and biological activity of a compound of interest. Table 1 provides definition for chemical abbreviations used herein. Table 1. Definitions of chemical abbreviations. Symbol Meaning Abu α-aminobutyric acid Ac acyl group Acc 1-amino-1-cyclo(C3-C9)alkyl carboxylic acid A3c 1-amino-1cyclopropanecarboxylic acid A4c 1-amino-1-cyclobutanecarboxylic acid A5c 1-amino-1-cyclopentanecarboxylic acid A6c 1-amino-1-cyclohexanecarboxylic acid Aha 7-aminoheptanoic acid Ahx 6-aminohexanoic acid Attorney Docket No.: R2054-7034WO Aib α-aminoisobutyric acid Aic 2-aminoindan-2-carboxylic acid Ala or A Alanine β-Ala β-alanine Apc denotes the structure: H N NH O Apn 5-aminopentanoic acid (HN—(CH2)4—C(O) Arg or R Arginine hArg Homoarginine Asn or N Asparagine Asp or D aspartic acid Bal 3-benzothienylalanine Bip 4,4’-biphenylalanine, represented by the structure CH O H N C C H Bpa 4-benzoylphenylalanine 4-Br-Phe 4-bromo-phenylalanine Cha β –cyclohexylalanine hCha homo-cyclohexylalanine Chg Cyclohexylglycine Cys or C Cysteine hCys Homocysteine Attorney Docket No.: R2054-7034WO Dab 2,4-diaminobutyric acid Dap 2,3-diaminopropionic acid Dip β,β-diphenylalanine Doc 8-amino-3,6-dioxaoctanoic acid with the structure of: HON O O 2-Fua β-(2-furyl)-alanine Gaba 4-aminobutyric acid Gln or Q Glutamine Glu or E glutamic acid Gly or G Glycine His or H Histidine 3-Hyp trans-3-hydroxy-L-proline, i.e., (2S,3S)-3-hydroxy-pyrrolidine-2- carboxylic acid 4-Hyp 4-hydroxyproline, i.e., (2S,4R)-4-hydorxypyrrolidine-2-carboxylic acid Ile or 1 Isoleucine Leu or L Leucine hLeu Homoleucine Lys or K Lysine Met or M Methionine β-hMet β-homomethionine 1-Nal β-(1-naphthyl)alanine 2-Nal β-(2-naphthyl)alanine Nip nipecotic acid Nle Norleucine Ole octahydroindole-2-carboxylic acid Orn Ornithine 2-Pal β-(2-pyridiyl)alanine 3-Pal β-(3-pyridiyl)alanine 4-Pal β-(4-pyridiyl)alanine Attorney Docket No.: R2054-7034WO Pen Penicillamine Pff (S)-pentafluorophenylalanine Phe or F Phenylalanine hPhe homophenylalanine Pro or P Proline hProP Homoproline Ser or S Serine Tle tert-Leucine Taz β-(4-thiazolyl)alanine 2-Thi β-(2-thienyl)alanine 3-Thi β-(3-thienyl)alanine Thr or T Threonine Trp or W Tryptophan Tyr or Y Tyrosine D-(Et) Tyr has a structure of O N HOVal or V Valine Certain other abbreviations used herein are defined as follows: Boc: tert-butyloxycarbonyl Bzl: Benzyl DCM: Dichloromethane DIC: N,N-diisopropylcarbodiimide DIEA: diisopropylethyl amine Dmab: 4-{N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl)- amino}benzyl Attorney Docket No.: R2054-7034WO DMAP: 4-(dimethylamino)pyridine DMF: Dimethylformamide DNP: 2,4-dinitrophenyl Fm: Fluorenylmethyl Fmoc: fluorenylmethyloxycarbonyl For: Formyl HBTU: 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate cHex Cyclohexyl HOAT: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HOBt: 1-hydroxy-benzotriazole MBNA 4-methylbenzhydrylamine Mmt: 4-methoxytrityl NMP: N-methylpyrrolidone O-tBu oxy-tert-butyl Pbf: 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl PyBroP bromo-tris-pyrrolidino-phosphonium hexafluorophosphate tBu: tert-butyl TIS: triisopropyIsilane TOS: Tosyl Trt Trityl TFA: trifluoro acetic acid TFFH: tetramethylfluoroforamidiaium hexafluorophosphate Z: benzyloxycarbonyl Unless otherwise indicated, with the exception of the N-terminal amino acid, all abbreviations (e.g. Ala) of amino acids in this disclosure stand for the structure of -NH-C(R)(R′)-CO-, wherein R and R′ each is, independently, hydrogen or the side chain of an amino acid (e.g., R═CH3and R′═H for Ala), or R and R′ may be joined to form a ring system. Attorney Docket No.: R2054-7034WO For the N-terminal amino acid, the abbreviation stands for the structure The designation “NH2” in e.g., as in Ac-Nle-c(Cys-D-Ala-His-D-Phe- NH2 (SEQ ID NO:13), indicates that the C-terminus of the peptide is amidated. Ac-Nle-c(Cys-D-Ala- His-D-Phe-Arg-Trp-Cys) (SEQ ID NO:107), or alternatively Ac-Nle-c(Cys-D-Ala-His-D-Phe- Arg-Trp-Cys)-OH (SEQ ID NO:107), indicates that the C-terminus is the free acid. “-c(Cys-Cys)-” or “-cyclo(Cys-Cys)-” denotes the structure: “-c Pen)-” denotes the structure: Lys)-” denotes the structure: are used throughout the disclosure: “Hydantoin-(C(O)-(Aa-Ab))” denotes the structure: and amino acid “Ab” the structure: . Attorney Docket No.: R2054-7034WO For example, “Hydantoin-(C(O)-Arg-Ab))” would have the following structure: NH2HN NH A3 4 -A - Cys]-” would have the following the structure: whereas a compound represented as “c[Hydantoin(C(O)-(Ab-Cys))-A1-A2-A3-A4-Cys]-” would have the structure: . For further guidance, “c[Hydantoin(C(O)-(Asp-Ab))-A1-A2-A3-A4-Lys]-” represents the following compound: Attorney Docket No.: R2054-7034WO substituted heteroalkyl, alkenyl, substituted alkenyl, aryl, alkylaryl, or substituted alklyaryl, and is indicated in the general formula of a particular embodiment as “Ac”. “Alkyl” refers to a hydrocarbon group containing one or more carbon atoms, where multiple carbon atoms if present are joined by single bonds. The alkyl hydrocarbon group may be straight-chain or contain one or more branches or cyclic groups. “Hydroxyalkyl” refers to an alkyl group wherein one or more hydrogen atoms of the hydrocarbon group are substituted with one or more hydroxy radicals, such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl and the like. “Substituted alkyl” refers to an alkyl wherein one or more hydrogen atoms of the hydrocarbon group are replaced with one or more substituents selected from the group consisting of halogen, (i.e., fluorine, chlorine, bromine, and iodine), -OH, -CN, -SH, amine (e.g., -NH2, -NHCH3), -NO2, guanidine, urea, amidine, and -(C1-C20) alkyl, wherein said -(C1- C20) alkyl optionally may be substituted with one or more substituents selected, independently for each occurrence, from the group consisting of halogens, —CF3, —OCH3, —OCF3, and -(CH2)0-20-COOH. In different embodiments 1, 2, 3 or 4 substituents are present. The presence of -(CH2)0-20-COOH results in the production of an alkyl acid. Non-limiting examples of alkyl acids containing, or consisting of, -(CH2)0-20-COOH include 2-norbornane acetic acid, tert-butyric acid, 3-cyclopentyl propionic acid, and the like. The term “halo” encompasses fluoro, chloro, bromo and iodo. Attorney Docket No.: R2054-7034WO Guanidines are a group of organic compounds that share a common functional group with the general structure (R1R2N)(R3R4N)C=N-R5. The central bond within this group is an imine, and the group is related structurally to amidines and ureas. “Heteroalkyl” refers to an alkyl wherein one of more of the carbon atoms in the hydrocarbon group is replaced with one or more of the following groups: amino, amido, —O—, —S— or carbonyl. In different embodiments 1 or 2 heteroatoms are present. “Substituted heteroalkyl” refers to a heteroalkyl wherein one or more hydrogen atoms of the hydrocarbon group are replaced with one or more substituents selected from the group consisting of halogen, (i.e., fluorine, chlorine, bromine, and iodine), -OH, —CN, —SH, —NH2, —NHCH3, —NO2, and -(C1-C20) alkyl, wherein said -(C1-C20) alkyl optionally may be substituted with one or more substituents selected, independently for each occurrence, from the group consisting of halogens, —CF3, -OCH3, -OCF3, and -(CH2)0-20-COOH. In different embodiments 1, 2, 3 or 4 substituents are present. “Alkenyl” refers to a hydrocarbon group made up of two or more carbons where one or more carbon-carbon double bonds are present. The alkenyl hydrocarbon group may be straight- chain or contain one or more branches or cyclic groups. “Substituted alkenyl” refers to an alkenyl wherein one or more hydrogens are replaced with one or more substituents selected from the group consisting of halogen (i.e., fluorine, chlorine, bromine, and iodine), —OH, —CN, —SH, —NH2, —NHCH3, —NO2, and -(C1-C20) alkyl, wherein said -(C1-C20) alkyl optionally may be substituted with one or more substituents selected, independently for each occurrence, from the group consisting of halogens, —CF3, — OCH3, —OCF3, and —(CH2)0-20—COOH. In different embodiments 1, 2, 3 or 4 substituents are present. “Aryl” refers to an optionally substituted aromatic group with at least one ring having a conjugated pi-electron system, containing up to three conjugated or fused ring systems. Aryl includes carbocyclic aryl, heterocyclic aryl and biaryl groups. Preferably, the aryl is a 5- or 6- membered ring. Preferred atoms for a heterocyclic aryl are one or more sulfur, oxygen, and / or nitrogen. Non-limiting examples of aryl include phenyl, 1-naphthyl, 2-naphthyl, indole, quinoline, 2-imidazole, 9-anthracene, and the like. Aryl substituents are selected from the group consisting of -(C1-C20) alkyl, -(C1-C20) alkoxy, halogen (i.e., fluorine, chlorine, bromine, and iodine), —OH, —CN, —SH, —NH2, -NO2, -(C1-C20) alkyl substituted with halogens, —CF3, — Attorney Docket No.: R2054-7034WO OCF3, and —(CH2)0-20—COOH. In different embodiments the aryl contains 0, 1, 2, 3, or 4 substituents. “Alkylaryl” refers to an “alkyl” joined to an “aryl”. The term “(C1-12)hydrocarbon moiety” encompasses alkyl, alkenyl and alkynyl and in the case of alkenyl and alkynyl there is C2-C12. For the avoidance of doubt, unless otherwise indicated, the term substituted means substituted by one or more defined groups. In the case where groups may be selected from a number of alternative groups, the selected groups may be the same or different. For the avoidance of doubt, the term independently means that where more than one substituent is selected from a number of possible substituents, those substituents may be the same or different. Designation “(amino acid)n” means that an amino acid is repeated n times. For example, designation “(Pro)2” or “(Arg)3” mean that proline or arginine residues are repeated, respectively, two or three times. MC4R agonists Described herein are methods for treating and / or preventing a disease, disorder, or condition, such as obesity or an obesity-related disorder (e.g., a metabolic disorder) in a subject, comprising administering a combination therapy to a subject comprising a melanocortin 4 receptor (MC4R) agonist and a SURx / Kirxchannel activator compound. Examples of naturally occurring MC4R agonists include α-MSH, β-MSH, γ-MSH and adenocorticitropic hormone (ACTH) or a functional fragment thereof. Examples of synthetic MC4R agonists are described in detail below. In some embodiments, an MC4R agonist can be any known agonist of MC4R. In some example embodiment, the MC4R agonist is not an adrenocorticotropic hormone (ACTH) or a fragment thereof. Exemplary MC4R agonists include those described in WO2011104378; WO2011104379; WO201060901; WO200887189, WO200887188, WO200887187, WO200887186; US20110065652; WO2010144341; WO2010144344; WO201065799; WO201065800; WO201065801; WO201065802; WO201037081; WO2009152079; WO2009151383; US20100311648; US20100280079; WO201081666; WO201034500; WO200910299; WO2008116665; WO201052256; WO201052255; WO201126015; US20100120783; WO201096854; US20100190793; WO201025142; WO2014144260; Attorney Docket No.: R2054-7034WO WO2017059075; and WO201015972. Further examples of MC4R agonists are found in U.S. Pat. No.8,263,608; U.S. Pat. No.8,247,530; U.S. Pat. No.8,114,844; and U.S. Pat. No. 7,968,548. The entire teachings of these publications are incorporated herein by reference. In some embodiments, the MC4R agonist is a compound of any one of Formulas (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII), or a pharmaceutically acceptable salt thereof as described herein. In some embodiments, the MC4R agonist is a compound of any one of Formulas (I) or (II), or a pharmaceutically acceptable salt thereof as described herein. In one embodiment, the MC4R agonist is a compound of Formula (I). In one embodiment, the MC4R agonist is a compound of Formula (II). In one example embodiment, the agonist of MC4R is a tripeptide D-Phe-Arg-Trp (SEQ ID NO: 560) or a pharmaceutical salt thereof. In another example, the agonist is any peptide that includes SEQ ID NO: 560 or a pharmaceutical salt thereof. In yet another example, the MC4R agonist is an acetylated tripeptide Ac-D-Phe-Arg-Trp-NH2(SEQ ID NO: 561) or a pharmaceutical salt thereof. In some embodiments, the MC4R agonist is a compound of Formula (I): (R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1(I) or a pharmaceutically acceptable salt thereof, wherein A1is Acc, HN—(CH2)m—C(O), L- or D- amino acid, or deleted; A2is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp, or Glu; A3is Gly, Ala, β-Ala, Gaba, Aib, D-amino acid, or deleted; A4is His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, or (X1, X2, X3, X4, X5)Phe; A5is D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X1, X2, X3, X4, X5)Phe, L- R5))-C(O); A7 Ala, Acc, Ala, 13-Ala, Gaba, Apn, Ahx, Aha, HN-(CH2)s-C(O), or deleted; A9is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn, or Lys; A10is Acc, HN-(CH2)t-C(O), L- or D-amino acid, or deleted; R1is OH or NH2; each of R2and R3is, independently for each occurrence, selected from the group consisting of H, (C1-C30)alkyl, (C1-C30)heteroalkyl, (C1-C30)acyl, (C2-C30)alkenyl, (C2- C30)alkynyl, aryl(C1-C30)alkyl, aryl(C1-C30)acyl, substituted (C1-C30)alkyl, substituted (C1- C30)heteroalkyl, substituted (C1-C30)acyl, substituted (C2-C30)alkenyl, substituted (C2- C30)alkynyl, substituted aryl(C1-C30)alkyl, and substituted aryl(C1-C30)acyl; each of R4and R5is, independently for each occurrence, H, (C1-C40)alkyl, (C1-C40)heteroalkyl, (C1-C40)acyl, (C2- C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, aryl(C1-C40)acyl, substituted (C1-C40)alkyl, Attorney Docket No.: R2054-7034WO substituted (C1-C40)heteroalkyl, substituted (C1-C40)acyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, substituted aryl(C1-C40)alkyl, substituted aryl(C1-C40)acyl, (C1- C40)alkylsulfonyl, or -C(NH)-NH2; m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7; n is, independently for each occurrence, 1, 2, 3, 4 or 5; s is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7; t is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7; X′, X2, X3, X4, and X5each is, independently for each occurrence, H, F, Cl, Br, I, -(C1-C10) alkyl, substituted (C1- C10) alkyl, (C2-C10) alkenyl, substituted (C2-C10) alkenyl, (C2-C10) alkynyl, substituted (C2-C10) alkynyl, aryl, substituted aryl, OH, NH2 , NO2 , or CN. In some embodiments, for Formula (I), when R4is (C1-C40)acyl, aryl(C1-C40)acyl, substituted (C1-C40)acyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl, or -C(NH)-NH2, then R5is H or (C1-C40)alkyl, (C1-C40)heteroalkyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1- C40)alkyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, or substituted aryl(C1-C40)alkyl. In some embodiments, for Formula (I), when R2is (C1-C30)acyl, aryl(C1-C30)acyl, substituted (C1-C30)acyl, or substituted aryl(C1-C30)acyl, then R3is H, (C1-C30)alkyl, (C1- C30)heteroalkyl, (C2-C30)alkenyl, (C2-C30)alkynyl, aryl(C1-C30)alkyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C2-C30)alkenyl, substituted (C2-C30)alkynyl, or substituted aryl(C1-C30)alkyl; In some embodiments, for Formula (I), either A3or A8or both must be present in said compound. In some embodiments, for Formula (I) when A2is Cys, D-Cys, hCys, D-hCys, Pen, or D- Pen, then A9is Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen. In some embodiments, for Formula (I), when A2is Asp or Glu, then A9is Dab, Dap, Orn, or Lys. In some embodiments, for Formula (I), when A8is Ala or Gly, then A1is not NIe. In some embodiments, for Formula (I), when A1is deleted, then R2and R3cannot both be H. In some embodiments, for Formula (I): A1is A6c, Arg, D-Arg, Cha, D-Cha, hCha, Chg, D-Chg, Gaba, Ile, Leu, hLeu, Met, β-hMet, 2-Nal, D-2-Nal, Nip, Nle, Oic, Phe, D-Phe, hPhe, hPro, Val, or deleted; A2is Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, or D-Pen; A3is D-Abu, Aib, Ala, β-Ala, D-Ala, D-Cha, Gaba, D-Glu, Gly, D-Ile, D-Leu, D-Tle, D-Val, or deleted;A4is Attorney Docket No.: R2054-7034WO His or 3-Pal; A5is D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-Trp, or D-(Et)Tyr; A6is Arg, or hArg; A7is Bal, Bip, 1-Nal, 2-Nal, Trp, D-Trp; A8is A6c, D-Ala, Aha, Ahx, Ala, β-Ala, Apn, Gaba, Gly or deleted; A9is Cys, D-Cys, hCys, D-hCys, Lys, Pen, or D-Pen; and A10is Thr, or deleted, wherein at least one of A3or A8is deleted, but not both. In some embodiments, the compound of Formula (I) is a compound disclosed in International Patent Application Publication Number WO 2007 / 008704, which is incorporated herein by reference in its entirety. In some embodiments, the compound of Formula (I) is selected from: (SEQ ID NO: 1) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 2) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; (SEQ ID NO: 3) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 4) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 5) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 6) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; (SEQ ID NO: 7) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 8) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; (SEQ ID NO: 9) Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 10) Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 11) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 12 ) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 13) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 14) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 15) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 16) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 17) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 18) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 19) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 20) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 21) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 22) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 23) Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 24) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 25) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 26) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 27) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 28) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 29) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 30) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 31) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 32) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 33) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 34) Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 35) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 36) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 37) Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 38) Ac-D-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 39) Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 40) Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 41) Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 42) Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 43) Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 44) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 45) n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 46) n-butyryl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 47) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 48) Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 49) Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 50) Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 51) Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 52) Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 53) Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 54) Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 55) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 56) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 57) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 58) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; (SEQ ID NO: 59) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; (SEQ ID NO: 60) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; (SEQ ID NO: 61) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 62) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 63) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; (SEQ ID NO: 64) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; (SEQ ID NO: 65) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 66) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 67) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 68) n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 69) n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 70) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 71) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 72) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; (SEQ ID NO: 73) Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 74) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 75) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; (SEQ ID NO: 76) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 77) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 78) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 79) D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 80) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 81) D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 82) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 83) D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 84) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 85) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 86) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; (SEQ ID NO: 87) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; (SEQ ID NO: 88) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 89) Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 90) Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)- NH2; (SEQ ID NO: 91) Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 92) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 93) Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 94) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 95) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 96) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 97) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 98) Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 99) Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 100) Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 101) Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 102) Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 103) Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 104) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 105) Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 106) Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 107) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; (SEQ ID NO: 108) Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)- NH2; (SEQ ID NO: 109) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; (SEQ ID NO: 110) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 111) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 112) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 113) Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 114) Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 115) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; (SEQ ID NO: 116) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 117) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; (SEQ ID NO: 118) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; (SEQ ID NO: 119) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; (SEQ ID NO: 120) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; (SEQ ID NO: 121) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; (SEQ ID NO: 122) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 123) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 124) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 125) Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 126) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 127) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 128) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 129) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; (SEQ ID NO: 130) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; (SEQ ID NO: 131) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; (SEQ ID NO: 132) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; (SEQ ID NO: 133) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; (SEQ ID NO: 134) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; (SEQ ID NO: 135) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; (SEQ ID NO: 136) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; (SEQ ID NO: 137) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; (SEQ ID NO: 138) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; (SEQ ID NO: 139) Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 140) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 141) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 142) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 143) Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 144) Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 145) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 146) Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; and (SEQ ID NO: 147) Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2, Attorney Docket No.: R2054-7034WO or a pharmaceutically acceptable salt thereof. In embodiments, the compound of Formula (I) is Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 140) or a pharmaceutically acceptable salt thereof. Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2(SEQ ID NO: 140), also known as RM-493 and setmelanotide, is a peptide that retains the specificity and functionality of the naturally occurring hormone that activates MC4R and has not been shown to adversely affect blood pressure in clinical trials (see, e.g., Chen et al. J. Clin. Endocrinol. Metab.2015;100(4):1639-45. The structure of Ac-Arg-c(Cys-D-Ala-His-D-Phe- Arg-Trp-Cys)-NH2 (SEQ ID NO: 140) is shown below: . In H-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-NH2(I-a) or a pharmaceutically acceptable salt thereof, wherein A1is Phe, D-Phe, or Nle; A2is Cys; A3is deleted; A4is His; A5is D-Phe or D-(Et)Tyr; A6is Arg or hArg; A7is Trp or Bip; A8is Ala, β-Ala, Gaba, or Apn; A9is D-Cys; and A10is Thr or deleted. In some embodiments, the compound of Formula (I-a) is selected from: (SEQ ID NO: 4) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 5) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 6) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; (SEQ ID NO: 79) D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 80) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 81) D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 82) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 83) D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 84) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 85) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; and (SEQ ID NO: 105) Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2. In some embodiments, the MC4R agonist is a compound of Formula (I-b): Ac-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-NH2 (I-b) or a pharmaceutically acceptable salt thereof, wherein: A1is Nle, A6c, D-2-Nal, Cha, Oic, Chg, hCha, D-Cha, D-hCha, Nip, hPro, hLeu, Phe, D-Phe, D- Chg, hPhe, β-hMet, Gaba, Leu, Ile, Val, 2-Nal, Arg or D-Arg; A2is Asp, Cys, D-Cys, or Pen; A3is D-Ala, β-Ala, Gaba, Aib, Gly, Ala, D-Glu, D-Abu, D-Val, D-Ile, D-Leu, D-Tle, D-Cha, deleted; A4His or 3-Pal; A5is Phe, D-Phe, or D-2-Nal; A6is Arg; A7is Trp, 1-Nal, 2-Nal, Bal, or D-Trp; A8is β-Ala, A6c, Ahx, Apn, Gaba, Ala, Aha, D-Ala or deleted; A9is Lys, Cys, D-Cys, or Pen; A10is deleted, wherein A2and A9are pairwise selected to form a disulfide or lactam bridge. In some embodiments, the compound of Formula (I-b) is selected from: (SEQ ID NO: 1) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 2) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; (SEQ ID NO: 3) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 7) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 8) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; (SEQ ID NO: 9) Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 10) Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 11) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 12 ) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 13) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 14) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 15) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 16) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 17) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 18) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 19) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 20) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 21) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 22) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 23) Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 24) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 25) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 26) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 27) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 28) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 29) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 30) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 31) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 32) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 33) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 34) Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 35) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 36) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 37) Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 38) Ac-D-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 39) Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 40) Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 41) Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 42) Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 43) Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 44) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 47) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 48) Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 49) Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 50) Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 51) Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 52) Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 53) Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 54) Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 55) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 56) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 57) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 58) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; (SEQ ID NO: 59) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; (SEQ ID NO: 60) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; (SEQ ID NO: 61) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 62) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 63) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; (SEQ ID NO: 64) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; (SEQ ID NO: 65) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 66) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 67) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 70) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 71) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 72) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; (SEQ ID NO: 73) Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 74) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 75) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; (SEQ ID NO: 76) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 77) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 78) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 86) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; (SEQ ID NO: 87) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; (SEQ ID NO: 89) Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 90) Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)- NH2; (SEQ ID NO: 91) Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 92) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 93) Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 94) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 95) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 96) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 97) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 98) Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 99) Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 100) Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 101) Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 102) Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 103) Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 106) Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 108) Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)- NH2; (SEQ ID NO: 109) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; (SEQ ID NO: 110) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 111) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 112) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 113) Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 114) Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 139) Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 140) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 141) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 142) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 143) Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 144) Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 145) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 146) Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; and (SEQ ID NO: 147) Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2. In some embodiments, the MC4R agonist is a compound of Formula (I-c): Ac-Nle-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-NH2(I-c) or a pharmaceutically acceptable salt thereof, wherein: A2is Asp, Cys, D-Cys, or Pen; A3is D- Ala, β-Ala, Gaba, Aib, Gly, Ala, Aib, Dl-Glu, D-Abu, D-Val, D-Ile, D-Leu, D-Tle, D-Cha, or deleted; A4is His or 3-Pal; A5is D-Phe, D-2-Nal, or Phe; A6is Arg; A7is Trp, D-Trp, 2-Nal, 1- Nal, Bal; A8is β-Ala, A6c, Ahx, Apn, Gaba, D-Ala, Aha, Ala or deleted; A9is Lys, Cys, D-Cys or Attorney Docket No.: R2054-7034WO Pen; and A10is deleted, wherein A2and A9are pairwise selected to form a disulfide or lactam bridge. In some embodiments, the compound of Formula (I-c) is selected from: (SEQ ID NO: 1) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 2) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; (SEQ ID NO: 3) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 7) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 8) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; (SEQ ID NO: 12 ) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 13) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 14) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 15) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 16) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 17) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 18) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 19) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 20) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 21) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 22) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 23) Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 24) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 25) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 26) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 27) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 28) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 29) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 30) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 31) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 32) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 33) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 55) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 56) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 57) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 58) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; (SEQ ID NO: 59) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; (SEQ ID NO: 60) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; (SEQ ID NO: 61) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 62) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 63) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; (SEQ ID NO: 64) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; (SEQ ID NO: 65) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 66) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 67) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 70) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 71) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 72) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; (SEQ ID NO: 73) Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 74) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 75) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; (SEQ ID NO: 76) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 77) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 78) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 86) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; (SEQ ID NO: 87) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; (SEQ ID NO: 89) Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 90) Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)- NH2; (SEQ ID NO: 91) Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 92) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 93) Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 94) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 95) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 96) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 97) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 106) Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 108) Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)- NH2; (SEQ ID NO: 109) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; (SEQ ID NO: 110) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 111) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; and (SEQ ID NO: 112) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2. In some embodiments, the MC4R agonist is a compound of Formula (I-d): H-D-Phe-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-NH2(I-d) or a pharmaceutically acceptable salt thereof, wherein A2is Cys; A3is deleted; A4is His; A5is D- Phe or D-(Et)Tyr; A6is Arg or hArg; A7is Trp or Bip; A8is Ala, β-Ala, or Gaba; A9is D-Cys; nd A10is Thr. In some embodiments, the compound of Formula (I-d) is selected from: (SEQ ID NO: 4) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 5) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 6) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; (SEQ ID NO: 79) D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 80) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 81) D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 82) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 83) D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; and (SEQ ID NO: 84) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2. In some embodiments, the MC4R agonist is a compound of Formula (II): R2 On-cyclo(A1-A2-A3-A4-A5-A6-A7)-R4(II), or a thereof, wherein: Attorney Docket No.: R2054-7034WO Orn, X4, X5) X5)Phe; A5is Arg, hArg, Dab, Dap, Lys or Orn; A6is Bal, 1-Nal, 2-Nal, (X1, X2, X3, X4, X5)Phe or Trp; A7is Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen or D-Pen; R1is H, (C1-C10)alkyl or substituted (C1-C10)alkyl; R2and R3each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl or R2and R3may be fused together form a cyclic moiety; R4is OH, NH2, CO2 H or C(O)NH2; R5and R6each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1- C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1- C5)alkyl or R5and R6may be fused together form a cyclic moiety; R7and R8each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl; or R7and R8may be fused together form a cyclic moiety; R9is H, (C1-C10)alkyl or substituted (C1-C10)alkyl; and n is, independently for each occurrence thereof, 0, 1, 2, 3, 4, 5, 6 or 7; or a pharmaceutically acceptable salt thereof. In some embodiments of Formula (II), A1is Cys; A2is D-Ala, Asn, Asp, Gln, Glu or D- Phe; A3is H is; A4is D-2-Nal or D-Phe; A5is Arg; A6is Trp; and A7is Cys or Pen; each of R′, R2, R3, and R9is, independently, H; R4is C(O)NH2; each of R5and R6is, independently, H, (C1- C10)heteroalkyl, substituted (C1-C10)alkyl or substituted (C1-C10)heteroalkyl or R5and R6may be fused together form a cyclic moiety; and each of R7and R8is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, substituted (C1-C10)alkyl or substituted (C1-C10)heteroalkyl; or pharmaceutically acceptable salts thereof. In some embodiments, the compound of Formula (II) is selected from: (SEQ ID NO: 148) Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 149) Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 150) Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 151) Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 152) Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 153) Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 154) Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 155) Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 156) Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 157) Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 158) Hydantoin(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 159) Hydantoin(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 160) Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 161) Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 162) Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 163) Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 164) Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 165) Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 166) Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)- NH2; (SEQ ID NO: 167) Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 168) Hydantoin(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 169) Hydantoin(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 170) Hydantoin(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 171) Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 172) Hydantoin(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 173) Hydantoin(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 174) Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 175) Hydantoin(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 176) Hydantoin(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 177) Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 178) Hydantoin(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 179) Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 180) Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 181) Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 182) Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 183) Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 184) Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 185) Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)- NH2; and (SEQ ID NO: 186) Hydantoin(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (II) is described in WO2008 / 147556 or International Patent Application Number PCT / US08 / 06675, each of which is incorporated herein by reference in its entirety. In embodiments, the compound of Formula (II) is hydantoin(C(O)-(Arg-Gly))-c(Cys- Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 148) or a pharmaceutically acceptable salt thereof, also known as RM-511. The structure of hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D- Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO:148) is shown below: H2N OOH2 R5X or a pharmaceutically the group consisting of -CH2-S-S-CH2-, -C(CH3)2-S-S-CH2-, -CH2-S-S-C(CH3)2-, -C(CH3)2-S-S-C(CH3)2-, -(CH2)2-S-S- CH2-, -CH2-S-S-(CH2)2-, -(CH2)2-S-S-(CH2)2-, -C(CH3)2-S-S-(CH2)2-, -(CH2)2-S-S-C(CH3)2-, - (CH2)t-C(O)-NR8-(CH2)r-and -(CH2)r-NR8-C(O)-(CH2)t-; R2each is, independently, H, (C1- Attorney Docket No.: R2054-7034WO C10)alkyl or substituted (C1-C10)alkyl; R3is -OH or -NH2; R4and R5each is, independently, H,(C1-C10)alkyl or substituted (C1-C10) H is, 2-Pal, 3-Pal, 4-Pal, (X1,X2, X3, X4, X5)Phe, Taz, 2-Thi, 3-Thi or A2 is D-Bal, D-1-Nal, D-2-Nal, D-Phe or A3is Arg, hArg, Dab, Dap, Lys or Orn; A4is Bal, 1-Nal, 2-Nal, (X1, X2, X3, X4, X5)Phe or Trp; R6and R7each is, independently for each occurrence thereof, H, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl provided that R6and R7may be joined together to form a ring; R8is H, (C1-C10)alkyl or substituted (C1-C10)alkyl; r is, independently for each occurrence thereof, 1, 2, 3, 4 or 5; and t is, independently for each occurrence thereof, 1 or 2. Compounds according to the foregoing formula can include compounds wherein X1is selected from the group consisting of: , . Patent Publication WO 2008 / 147556 or International Patent Application Number PCT / US08 / 06675, each of which is incorporated herein by reference in its entirety. In some embodiments, the compound of Formula (III) is selected from: (SEQ ID NO: 187) c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 188) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 189) c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 190) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (SEQ ID NO: 191) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 192) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (SEQ ID NO: 193) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (SEQ ID NO: 194) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (SEQ ID NO: 195) c[Hydantoin(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2; (SEQ ID NO: 196) c[Hydantoin(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 197) c[Hydantoin(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 198) c[Hydantoin(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 199) c[Hydantoin(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 200) c[Hydantoin(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2; (SEQ ID NO: 201) c[Hydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2; (SEQ ID NO: 202) c[Hydantoin(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2; (SEQ ID NO: 203) c[Hydantoin(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 204) c[Hydantoin(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 205) c[Hydantoin(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2; (SEQ ID NO: 206) c[Hydantoin(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2; (SEQ ID NO: 207) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (SEQ ID NO: 208) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (SEQ ID NO: 209) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (SEQ ID NO: 210) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2; (SEQ ID NO: 211) c[Hydantoin(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH2; and (SEQ ID NO: 212) c[Hydantoin(C(O)-(Glu-His))-D-Phe-Arg-Trp-Lys]-NH2, or a pharmaceutically acceptable salt thereof. In some embodiments, the MC4R agonist is a compound of Formula (IV): (R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-NH2(IV) or a pharmaceutically acceptable salt thereof, wherein A1is Nle or deleted; A2is Cys or Asp; A3is Glu or D-Ala; A4is His; A5is D-Phe; A6is Arg; A7is Trp, 2-Nal or Bal; A8is Gly, Ala, D-Ala, 3-Ala, Gaba or Apn; A9is Cys or Lys; each of R2and R3is independently selected from the group consisting of H or (C1-C6)acyl. Attorney Docket No.: R2054-7034WO In exemplary embodiments of Formula (IV): (I) when R2is (C1-C6)acyl, then R3is H; and (II) when A2is Cys, then A9is Cys. Exemplary MC4R agonists of Formula (IV) are disclosed in International Patent Application Publication Number WO 2007 / 008704, which is incorporated herein by reference in its entirety. In some embodiments, the compound of Formula (IV) is selected from: (SEQ ID NO: 213) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2; (SEQ ID NO: 214) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2; (SEQ ID NO: 215) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; (SEQ ID NO: 216) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 217) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 218) Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; (SEQ ID NO: 219) Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; (SEQ ID NO: 220) Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; (SEQ ID NO: 221) Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; (SEQ ID NO: 222) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; and (SEQ ID NO: 223) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2, or a pharmaceutically acceptable salt thereof. In some embodiments, the MC4R agonist is a compound of Formula (V): (R2R3)-B1-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-A11-A12-A13-B2-B3-R1(V) or a pharmaceutically acceptable salt thereof: B1is a peptide moiety which contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids, wherein at least 5 amino acids are independently selected from the group consisting of L-Arg, D-Arg, L-hArg and D-hArg, or B1is optionally deleted; A1is Acc, HN-(CH2)m-C(O), L- or D-amino acid or deleted; A2is Cys, D-Cys, hCys, D-hCys, Pen, D- Pen, Asp or Glu; A3is Gly, Glu, Ala, β-Ala, Gaba, Aib, D-amino acid or deleted; A4is H is, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi or (X′, X2, X3, X4, X5)Phe; A5is D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X1, X2, X3, X4, X5)Phe, D-(Et)Tyr, D-Dip, D-Bip or D-Bpa; A6is Arg, hArg, Dab, D- Attorney Docket No.: R2054-7034WO acid or deleted; A11is Pro, hPro, 3-Hyp, 4-Hyp or deleted; A12is Lys, Dab, Dap, Arg, hArg or deleted; A13is Asp, Glu or deleted; B2is a peptide moiety containing 1, 2, 3, 4, or 5 amino acids or deleted, B3is a peptide moiety which contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acids wherein at least 5 amino acids are independently selected from the group consisting of L- Arg, D-Arg, L-hArg and D-hArg, or is deleted; R1is OH or NH2; R2and R3each is, independently for each occurrence, selected from the group consisting of H, (C1-C30)alkyl, (C1- C30)heteroalkyl, (C1-C30)acyl, (C2-C30)alkenyl, (C2-C30)alkynyl, aryl(C1-C30)alkyl, aryl(C1- C30)acyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C1-C30)acyl, substituted (C2-C30)alkenyl, substituted (C2-C30)alkynyl, substituted aryl(C1-C30)alkyl and substituted aryl(C1-C30)acyl; R4and R5each is, independently for each occurrence, H, (C1- C40)alkyl, (C1-C40)heteroalkyl, (C1-C40)acyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, aryl(C1-C40)acyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C1- C40)acyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, substituted aryl(C1-C40)alkyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl or C(NH)-NH2; n is, independently for each occurrence, 1, 2, 3, 4 or 5; m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7; s is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7; t is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7; X1, X2, X3, X4and X5each is, independently for each occurrence, H, F, Cl, Br, I, -(C1-C10) alkyl, substituted (C1-C10) alkyl, (C2-C10) alkenyl, substituted (C2-C10) alkenyl, (C2- C10) alkynyl, substituted (C2-C10) alkynyl, aryl, substituted aryl, OH, NH2, NO2or CN. In some embodiments of Formula (V): (I) when R4is (C1-C40)acyl, aryl(C1-C40)acyl, substituted (C1-C40)acyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl or C(NH)—NH2, then R5is H, (C1-C40)alkyl, (C1- C40)heteroalkyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl or substituted aryl(C1-C40)alkyl; (II) when R2is (C1-C30)acyl, aryl(C1-C30)acyl, substituted (C1-C30)acyl or substituted aryl (C1-C30)acyl, then R3is H, (C1-C30)alkyl, (C1-C30)heteroalkyl, (C2-C30)alkenyl, (C2-C30)alkynyl, aryl(C1-C30)alkyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C2- C30)alkenyl, substituted (C2-C30)alkynyl or substituted aryl(C1-C30)alkyl; (III) neither B1nor B2contains one or more of the following amino acid sequences: Arg- (Lys)2-(Arg)2-Gln-(Arg)3, Tyr-Ala-Arg-Lys-Ala-(Arg)2-Gln-Ala-(Arg)2, Tyr-Ala-Arg-(Ala)2- Attorney Docket No.: R2054-7034WO (Arg)2-(Ala)2-(Arg)2, Tyr-Ala-(Arg)9, Tyr-(Ala)3-(Arg)7, Tyr-Ala-Arg-Ala-Pro-(Arg)2-Ala-(Arg)3 or Tyr-Ala-Arg-Ala-Pro-(Arg)2-Pro-(Arg)2; (IV) either B1or B2or both must be present in said compound; (V) when A2is Cys, D-Cys, hCys, D-hCys, Pen or D-Pen, then A9is Cys, D-Cys, hCys, D-hCys, Pen or D-Pen; and (VI) when A2is Asp or Glu, then A9is Dab, Dap, Orn or Lys. In some embodiments of Formula (V): B1is Arg-Lys-Gln-Lys-(Arg)5, Arg-(Lys)2-Arg-Gln-(Arg)4, Arg-(Lys)2-(Arg)3-Gln-(Arg)2, Arg-(Lys)2-(Arg)4-Gln-Arg, Arg-(Lys)2-(Arg)5-Gln, Arg-(Lys)2-Gln-(Arg)5, Arg-Gln-(Lys)2- (Arg)5, Arg-Gln-(Arg)7, Arg-Gln-(Arg)8, (Arg)2-Gln-(Arg)6, (Arg)2-Gln-(Arg)7, (Arg)3-Gln- (Arg)5, (Arg)3-Gln-(Arg)6, (Arg)4-Gln-(Arg)4, (Arg)4-Gln-(Arg)5, (Arg)5, (Arg)5-Gln-(Arg)3, (Arg)5-Gln-(Arg)4, (Arg)6, (Arg)6-Gln-(Arg)3, (Arg)7, (Arg)7-Gln-(Arg)2, (Arg)8, (Arg)s-Gln-Arg, (Arg)9, (Arg)9-Gln, (D-Arg)5, (D-Arg)6, (D-Arg)7, (D-Arg)8, (D-Arg)9, Gln-Arg-(Lys)2-(Arg)5, Gln-(Arg)8, Gln-(Arg)9, Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3, Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln- (Arg)3-Doc; or deleted; B2is β-Ala, β-Ala-Gly, β-Ala-Tyr, β-Ala-Tyr-Gly, (β-Ala)2, (β-Ala)2-Gly, (β-Ala)2-Tyr, (β-Ala)2-Tyr-Gly, Doc, Doc-Gly, Doc-Tyr, Doc-Tyr-Gly, (Doc)2, (Doc)2-Gly, (Doc)2-Tyr, Doc)2- Tyr-Gly, or deleted; B3is Arg-Lys-Gln-Lys-(Arg)5, Arg-Lys-(Arg)3-Gln-(Arg)3, Arg-(Lys)2-Arg-Gln-(Arg)4, Arg-(Lys)2-Gln-(Arg)5, Arg-(Lys)2-(Arg)2-Gln-(Arg)3, Arg-(Lys)2-(Arg)3-Gln-(Arg)2, Arg-(Lys)2- (Arg)4-Gln-Arg, Arg-(Lys)2-(Arg)5-Gln, Arg-Gln-(Lys)2-(Arg)5, Arg-Gln-(Arg)7, Arg-Gln-(Arg)s, (Arg)2-Lys-(Arg)2-Gln-(Arg)3, (Arg)2-Gln-(Arg)6, (Arg)2-Gln-(Arg)7, (Arg)3-Gln-(Arg)5, (Arg)3- Gln-(Arg)6, (Arg)4-Gln-(Arg)4, (Arg)4-Gln-(Arg)5, (Arg)5, (Arg)s-Gln-(Arg)3, (Arg)5-Gln-(Arg)4, (Arg)6, (Arg)6-Gln-(Arg)3, (Arg)7, (Arg)7-Gln-(Arg)2, (Arg)8, (Arg)s-Gln-Arg, (Arg)9, (Arg)9-Gln, (D-Arg)5, (D-Arg)6, (D-Arg)7, (D-Arg)8, (D-Arg)9, Gln-Arg-(Lys)2-(Arg)5, Gln-(Arg)8, Gln- (Arg)9, or deleted; A1is A6c, Cha, hCha, Chg, D-Chg, hChg, Gaba, hLeu, Met, β-hMet, D-2-Nal, Nip, Nle, Oic, Phe, D-Phe, hPhe, hPro, or deleted; A2is Cys; A3is D-Abu, Aib, Ala, β-Ala, D-Ala, D-Cha, Gaba, Glu, Gly, D-Ile, D-Leu, D-Met, D- Nle, D-Phe, D-Tle, D-Trp, D-Tyr, D-Val, or deleted; Attorney Docket No.: R2054-7034WO A4is H; A5is D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-(X1, X2, X3, X4, X5)Phe, D-Trp, or D-(Et)Tyr; A6is Arg or hArg; A7is Bal, Bip, 1-Nal, 2-Nal, Trp, or D-Trp; A8is A5c, A6c, Aha, Ahx, Ala, β-Ala, Apn, Gaba, Gly, or deleted; A9is Cys, D-Cys, hCys, D-hCys, Lys, Pen, or D-Pen; A10is Pro, Thr or deleted; A11is Pro or deleted; A12is Arg, Lys, or deleted; A13is Asp or deleted; each of R2and R3is, independently, H or acyl; or pharmaceutically acceptable salts thereof. In some embodiments, the compound of Formula (V) is selected from: (SEQ ID NO: 224) Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Nle-c(Asp-His-D-2-Nal-Arg-Trp- Lys)-NH2; (SEQ ID NO: 225) Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc-Nle-c(Asp-His-D-2-Nal-Arg- Trp-Lys)-NH2; (SEQ ID NO: 226) Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln- (Arg)3-NH2; (SEQ ID NO: 227) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2- Gln-(Arg)3-NH2; (SEQ ID NO: 228) Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2- Gln-(Arg)3-NH2; (SEQ ID NO: 229) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg- (Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 230) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg- (Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 231) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-Arg-(Lys)2- (Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 232) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg- (Lys)2-(Arg)2-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 233) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly- Arg- (Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 234) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 235) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly- Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 236) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2- Gln-(Arg)3-NH2; (SEQ ID NO: 237) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 238) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 239) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 240) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 241) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (SEQ ID NO: 242) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-Gln-(Arg)5-NH2; (SEQ ID NO: 243) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2; (SEQ ID NO: 244) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2; (SEQ ID NO: 245) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Aib-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 246) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala- (Arg)5 -Gln-(Arg)3-NH2; (SEQ ID NO: 247) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)5-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 248) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 249) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 250) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 251) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 252) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6- Gln-(Arg)3-NH2; (SEQ ID NO: 253) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 254) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6- Gln-(Arg)3-NH2; (SEQ ID NO: 255) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2; (SEQ ID NO: 256) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-Gln-(Lys)2-(Arg)5-NH2; (SEQ ID NO: 257) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)5-Gln-NH2; (SEQ ID NO: 258) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 259) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 260) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 261) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg- Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 262) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 263) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 264) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 265) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 266) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 267) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 268) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 269) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 270) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 271) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg- Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 272) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 273) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2- Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 274) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg- Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 275) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 276) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 277) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 278) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly- Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 279) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 280) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 281) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 282) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 283) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5- Gln-(Arg)4-NH2; (SEQ ID NO: 284) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5- Gln-(Arg)4-NH2; (SEQ ID NO: 285) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 286) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 287) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 288) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 289) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala- (Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 290) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 291) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 292) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 293) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 294) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 295) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 296) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala- (Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 297) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 298) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 299) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 300) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 301) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 302) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 303) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 304) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 305) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5- Gln-(Arg)4-NH2; (SEQ ID NO: 306) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5- Gln-(Arg)4-NH2; (SEQ ID NO: 307) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 308) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 309) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 310) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr- Gly-(Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 311) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr- Gly-(Arg)6-Gln-(Arg)3-NH2; (SEQ ID NO: 312) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-Arg-(Lys)2- (Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 313) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2- Arg-Gln-(Arg)4-NH2; (SEQ ID NO: 314) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2- (Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 315) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 316) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 317) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 318) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 319) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)2-Lys- (Arg)2-Gln-(Arg)3-NH2; (SEQ ID NO: 320) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys- (Arg)3-Gln-(Arg)3-NH2; (SEQ ID NO: 321) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)2-Lys-(Arg)2- Gln-(Arg)3-NH2; (SEQ ID NO: 322) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)3- Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 323) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)2-Lys-(Arg)2-Gln- (Arg)3-NH2; (SEQ ID NO: 324) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)3-Gln- (Arg)3-NH2; (SEQ ID NO: 325) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 326) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 327) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 328) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3 -NH2; (SEQ ID NO: 329) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 330) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 331) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 332) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2 -Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 333) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 334) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 335) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5 -Gln- (Arg)4 -NH2; (SEQ ID NO: 336) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 337) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 338) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5- Gln-(Arg)4-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 339) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5 -Gln-(Arg)4 - NH2; (SEQ ID NO: 340) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 341) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 342) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 343) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 344) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2 -Tyr-Gly-(Arg)5 -Gln- (Arg)4 -NH2; (SEQ ID NO: 345) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly- (Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 346) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5 -Gln-(Arg)3 - NH2; (SEQ ID NO: 347) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3 -NH2; (SEQ ID NO: 348) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 349) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 350) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 351) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 352) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 353) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 354) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5 -Gln-(Arg)3 -NH2; (SEQ ID NO: 355) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 356) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5 -Gln-(Arg)3 -NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 357) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5 -Gln-(Arg)3 -NH2; (SEQ ID NO: 358) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 359) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2 -Gly-(Arg)5-Gln-(Arg)3 - NH2; (SEQ ID NO: 360) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 361) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 362) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 363) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 364) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2 -Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 365) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 366) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2 -(Arg)5 -Gln-(Arg)4 -NH2; (SEQ ID NO: 367) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 368) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4 -NH2; (SEQ ID NO: 369) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 370) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 371) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 372) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2 -(Arg)5 -Gln-(Arg)4 -NH2; (SEQ ID NO: 373) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2;(SEQ ID NO: 374) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)5 -Gln-(Arg)3 - NH2; (SEQ ID NO: 375) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 376) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)5 -Gln-(Arg)3 -NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 377) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5 - Gln-(Arg)3 - NH2; (SEQ ID NO: 378) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 379) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 380) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 381) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly- (Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 382) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 383) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 384) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5 -Gln-(Arg)3 - NH2; (SEQ ID NO: 385) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 386) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5 -Gln-(Arg)3 - NH2; (SEQ ID NO: 387) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3- NH2; (SEQ ID NO: 388) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 389) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2 -Tyr-Gly-(Arg)5 - Gln-(Arg)3 - NH2; (SEQ ID NO: 390) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 391) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 392) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3- NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 393) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2 -Tyr-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 394) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 395) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5 -Gln- (Arg)4-NH2; (SEQ ID NO: 396) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 397) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5- Gln-(Arg)4- NH2; (SEQ ID NO: 398) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 399) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)4 -NH2; (SEQ ID NO: 400) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5 -Gln-(Arg)4 - NH2; (SEQ ID NO: 401) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 402) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 403) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 404) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 405) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 406) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 407) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 408) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 409) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 410) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)5 -Gln-(Arg)3- NH2; (SEQ ID NO: 411) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr- Gly-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 412) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 413) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly -(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 414) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 415) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 416) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 417) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 418) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 419) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 420) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 421) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 422) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 423) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln- (Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 424) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 425) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 426) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 427) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 428) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 429) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2 -Tyr-Gly-(Arg)5 -Gln-(Arg)3-NH2; (SEQ ID NO: 430) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 431) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2 -Gly-(Arg)5 - Gln-(Arg)3-NH2; (SEQ ID NO: 432) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 433) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 434) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 435) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 436) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 437) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Tyr-Gly-(Arg)5 - Gln-(Arg)3-NH2; (SEQ ID NO: 438) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln- (Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 439) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Gly-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 440) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 441) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β- Ala-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 442) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 443) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 444) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 445) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 446) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5 -Gln- (Arg)3-NH2; (SEQ ID NO: 447) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 448) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β- Ala-Tyr-Gly- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 449) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 450) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 451) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5- Gln-(Arg)4-NH2; (SEQ ID NO: 452) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 453) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln- (Arg)4-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 454) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 455) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 456) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 457) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 458) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 459) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 460) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 461) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 462) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 463) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 464) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly- (Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 465) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 466) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 467) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 468) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 469) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 470) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 471) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 472) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 473) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 474) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 475) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 476) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 477) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 478) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 479) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 480) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 481) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 482) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 483) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 484) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 485) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 486) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 487) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 488) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 489) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 490) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 491) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 492) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 493) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 494) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 495) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 496) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 497) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 498) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)4- NH2; (SEQ ID NO: 499) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 500) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 501) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 502) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5- Gln-(Arg)3-NH2; (SEQ ID NO: 503) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 504) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 505) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 506) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 507) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 508) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 509) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 510) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5- Gln-(Arg)4-NH2; (SEQ ID NO: 511) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 512) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 513) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 514) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 515) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 516) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 517) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 518) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 519) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 520) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 521) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 522) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; (SEQ ID NO: 523) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 524) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3- NH2; (SEQ ID NO: 525) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 526) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)3-NH2; (SEQ ID NO: 527) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID NO: 528) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4- NH2; (SEQ ID NO: 529) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO: 530) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln- (Arg)4-NH2; and (SEQ ID NO: 531) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2, or pharmaceutically acceptable salts thereof. In some embodiments, a compound of Formula (V) is disclosed in International Application Publication Number WO 2007 / 008684, which is incorporated herein by reference in its entirety. In some embodiments, the MC4R agonist is a compound of Formula (VI): Ac-c(Cys-Glu-His-A1-Arg-A2-A3-Cys)-(Pro)2-Lys-Asp-NH2 (VI) or pharmaceutically acceptable salts thereof. In Formula (VI): A1is the D-isomer of X-Phe or 2-Nal where X is halogen; A2is Bal, 1-Nal, 2-Nal, or Trp; and A3is Aib, Ala, β-Ala or Gly, In some embodiments, the compound of Formula (VI) is selected from: (SEQ ID NO: 532) Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2; (SEQ ID NO: 533) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (SEQ ID NO: 534) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (SEQ ID NO: 535) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (SEQ ID NO: 536) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (SEQ ID NO: 537) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)2-Lys-Asp-NH2; and (SEQ ID NO: 538) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)2-Lys-Asp-NH2, or pharmaceutically acceptable salts thereof. Attorney Docket No.: R2054-7034WO In an example embodiment, the MC4R agonist is a compound of Formula (VII): R2O 7 X R3R or a X is selected - , -2-S-S-CH2-,-CH2-S- S-C(CH3)2-, -C(CH3)2-S-S-C(CH3)z-, -(CH2)2-S-S-CH2-, -CH2-S-S-(CH2)2, -(CH2)2-S-S-(CH2)2-, -C(CH3)2-S-S-(CH2)2-, -(CH2)2-S-S-C(CH3)2-, -(CH2)t-C(O)-NR8-(CH2)r- and -(CH2)r-NR8- C(O)-(CH2)t-; each of R1and R5is, independently, H, (C1-C10)alkyl or substituted (C1-C10)alkyl; each of R2and R3is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1- C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1- C5)alkyl or R2and R3may be fused together to form a ring; R4is OH or NH2; each of R6and R7is, independently, H, (C1-C10)alkyl or substituted (C1-C10)alkyl; A1is an L- or D-amino acid or deleted; A2is H is, 2-Pal, 3-Pal, 4-Pal, (X1, X2, X3, X4, X5)Phe, Taz, 2-Thi or 3-Thi; A3is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X1, X2, X3, X4, X5)Phe; A4is Arg, hArg, Dab, Dap, Lys or Orn; A5is Bal, 1-Nal, 2-Nal, (X1, X2, X3, X4, X5)Phe or Trp; r is, independently for each occurrence thereof, 1, 2, 3, 4 or 5; and t is, independently for each occurrence thereof, 1 or 2; or pharmaceutically acceptable salts thereof. In an example embodiment of the compounds of Formula (VII), A1is Ala, D-Ala, Asn, Asp, Gln, Glu or Gly. Example compounds according to Formula (VII) include: (SEQ ID NO: 539) c[Hydantoin(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 540) c[Hydantoin(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 541) c[Hydantoin(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 542) c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 543) c[Hydantoin(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 544) c[Hydantoin(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 545) c[Hydantoin(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 546) c[Hydantoin(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 547) c[Hydantoin(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 548) c[Hydantoin(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 549) c[Hydantoin(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID NO: 550) c[Hydantoin(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; and (SEQ ID NO: 551) c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2, or pharmaceutically acceptable salts thereof. In some embodiments, a compound of Formula (VII) is disclosed in International Application Publication Number WO2008 / 147556, which is incorporated herein by reference in its entirety. In some embodiments, the MC4R agonist is a compound of Formula (VIII): (R2R3)-A0-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1(VIII) or a pharmaceutically acceptable salt thereof wherein: A0is an aromatic amino acid A1is Acc, HN-(CH2)m-C(O), an L- or D-amino acid; A2is Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, or D-Pen; A3is Aib, Ala, β-Ala, Gaba, Gly or a D-amino acid; A4is H is, 2-Pal, 3-Pal, 4-Pal, (X1, X2, X3, X4, X5)Phe, Taz, 2-Thi, or 3-Thi; A5is D-Bal, D-1-Nal, D-2-Nal, D-Phe, L-Phe, D-(X1, X2, X3, X4, X5)Phe, L-Phe, D-Trp or D-(Et)Tyr; A6is Arg, hArg, Dab, Dap, Lys, Orn, or HN-CH((CH2)n-N(R4R5))-C(O); A7is Bal, D-Bal, Bip, D-Bip, 1-Nal, D-1-Nal, 2-Nal, D-2-Nal, or D-Trp; A8is Acc, Aha, Ahx, Ala, D-Ala, β-Ala, Apn, Gaba, Gly, HN-(CH2)s-C(O), or deleted; A9is Cys, D-Cys, hCys, D-hCys, Dab, Dap, Lys, Orn, Pen, or D-Pen; A10is Acc, HN-(CH2)t-C(O), L- or D-amino acid, or deleted; R1is OH, or NH2; Attorney Docket No.: R2054-7034WO each of R2and R3is, independently for each occurrence selected from the group consisting of H, (C1-C30)alkyl, (C1-C30)heteroalkyl, (C1-C30)acyl, (C2-C30)alkenyl, (C2- C30)alkynyl, aryl(C1-C30)alkyl, aryl(C1-C30)acyl, substituted (C1-C30)alkyl, substituted (C1- C30)heteroalkyl, substituted (C1-C30)acyl, substituted (C2-C30)alkenyl, substituted (C2- C30)alkynyl, substituted aryl(C1-C30)alkyl, and substituted aryl(C1-C30)acyl; each of R4and R5is, independently for each occurrence, H, (C1-C40)alkyl, (C1- C40)heteroalkyl, (C1-C40)acyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, aryl(C1- C40)acyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C1-C40)acyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, substituted aryl(C1-C40)allyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl, or -C(NH)-NH2;m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7; n is, independently for each occurrence, 1, 2, 3, 4 or 5; s is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7; t is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7; X1, X2, X3, X4, and X5each is, independently for each occurrence, H, F, Cl, Br, I, (C1- C10)alkyl, substituted (C1-C10)alkyl, (C2-C10)alkenyl, substituted (C2-C10)alkenyl, (C2- C10)alkynyl, substituted (C2-C10)alkynyl, aryl, substituted aryl, OH, NH2, NO2, or CN. In example embodiments of Formula (VIII) (I) when R4is (C1-C40)acyl, aryl(C1-C40)acyl, substituted (C1-C40)acyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl, or -C(NH)-NH2, then R5is H or (C1-C40)alkyl, (C1- C40)heteroalkyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, or substituted aryl(C1-C40)alkyl; (II) when R2is (C1-C30)acyl, aryl(C1-C30)acyl, substituted (C1-C30)acyl, or substituted aryl(C1-C30)acyl, then R3is H, (C1-C30)alkyl, (C1-C30)heteroalkyl, (C2-C30)alkenyl, (C2- C30)alkynyl, aryl(C1-C30)alkyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C2-C30)alkenyl, substituted (C2-C30)alkynyl, or substituted aryl(C1-C30)alkyl; (III) when A2is Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen, then A9is Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen; (IV) when A2is Asp or Glu, then A9is Dab, Dap, Orn, or Lys; Attorney Docket No.: R2054-7034WO (V) when A8is Ala or Gly, then A1is not Nle; or pharmaceutically acceptable salts thereof. In example embodiments of compounds of Formula (VIII): A0is 1-Nal, 2-Nal, H is, Pff, Phe, Trp, or Tyr; A1is Arg; A2is Cys; A3is D-Ala; A4is H; A5is D-Phe; A6is Arg; A7is Trp; A8is deleted; A9is Cys; and A10is deleted; or pharmaceutically acceptable salts thereof. Particular compounds of the immediately foregoing group of Formula (VIII) compounds include: (SEQ ID NO: 552) Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 553) Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 554) Ac-1-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 555) Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 556) Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 557) Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 558) H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; and (SEQ ID NO: 559) Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In some embodiments, the MC4R agonist is an agonist described in WO2014 / 144260 A1, incorporated herein by reference. In one example embodiment, an MC4R agonist is a compound represented by formula (IX): - A - A - A - - A - A - A - A - R R11 2 3A4 5 6 7 8 2, or a pharmaceutically acceptable salt thereof, wherein: R1is H, or a (C1-C6)acyl; R2is, -NR3R4, or –OR5wherein R3, R4, and R5are each independently is H or a (C1- C6)alkyl; A1is an amino acid residue selected from Arg, Lys, Orn, His, Nle, Phe, Val, Leu, Trp, Tyr, Ala, Ser, Thr, Gln, Asn, Asp, Glu, or TzAla; or A1is a moiety selected from an optionally substituted -(C1-C12)-alkyl, an optionally substituted -(C6-C18)-aryl, an optionally substituted -(C5-C18)-heteroaryl, an aralkyl wherein the Attorney Docket No.: R2054-7034WO aryl portion is an optionally substituted (C6-C18)aryl, and the alkyl portion is an optionally substituted (C1-C12)alkyl, or a heteroaralkyl, wherein the heteroaryl portion is an optionally substituted (C5-C18)heteroaryl, and the alkyl portion is an optionally substituted (C1-C12)alkyl; A2and A8is each independently an amino acid residue selected from Cys, hCys, Pen, Asp, Glu, Lys, Orn, Dbu, or Dpr, wherein A2and A8are pairwise selected so as to be able to form covalent bond between their respective side chains; A3is absent or is an amino acid residue selected from Ala, Tle, Val, Leu, Ile, Cha, Pro, Ser, Thr, Lys, Arg, His, Phe, Gln, Sar, Gly, Asn, Aib, or residue Y, wherein Y is an amino acid selected from amino acids represented by the following structural formulas CO H1NH2 2R1NH2CO2H 2H , R11and R12, each independently, is H, -CH3, phenyl, or benzyl; R21, R22, R23, and R24, each independently is H, -CH3, -CF3, phenyl, benzyl, F, Cl, Br, I, -OCH3, or -OH; R31, R32, R33, R34, R41, R42, and R43, each independently is H, -CH3, -CF3, phenyl, benzyl, F, Cl, Br, I, -OCH3, or -OH; A4is absent or is an amino acid residue selected from Atc, Ala, QAla, Aib, Sar, Ser, Thr, Pro, Hyp, Asn, Gln, an optionally substituted His, Trp, Tyr, Lys, Arg, sChp, or residue X, where the X is an amino acid selected from amino acids represented by the following formulas: Attorney Docket No.: R2054-7034WO H2N CO2H NH2CO2H5NH2CO2H R1, - or R61, R62, R63, and R64, each independently is H, -CH3, -CF3, phenyl, benzyl, F, Cl, Br, I, -OCH3, or -OH; R71, R72, R73, R74, R81, R82, and R83, each independently is H, -CH3, -CF3, phenyl, benzyl, F, Cl, Br, I, -OCH3, or -OH; A5is an optionally substituted Phe, an optionally substituted 1-Nal, or an optionally substituted 2-Nal; A6is Arg; and A7is Trp, wherein any amino acid residue is either in L- or in D-configuration. Exemplary compound of Formula (IX) include: (SEQ ID NO: 560) Ac-Arg-c(Cys-D-Ala-His-D-Phe(p-F)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 561) Ac-Arg-c(Cys-D-Ala-Pro-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 562) Ac-Arg-c(Cys-D-Ala-Pro-D-Phe(p-F)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 563) Ac-Arg-c(Cys-D-Ala-Pro-D-Phe(p-F)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 564) Ac-Arg-c(Cys-D-Ala-Ser-D-Phe(p-F)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 565) Ac-Arg-c(Cys-D-Ala-Thr-D-Phe(p-CN)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 566) Ac-Arg-c(Cys-D-Ala-Asn-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 567) Ac-Arg-c(Cys-D-Ala-Gln-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 568) Ac-Arg-c(Cys-D-Ala-Trp-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 569) Ac-Arg-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 570) Ac-Arg-c(Cys-D-Val-Gln-D-Phe-Arg-Trp-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 571) Ac-Arg-c(Cys-D-Val-Pro-D-Phe-Arg-Trp-Cys)-NH2; and (SEQ ID NO: 572) Ac-Arg-c(Cys-D-Ser-Pro-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In yet another embodiment, the polypeptides of the present invention include any one of the following structural formulas: (SEQ ID NO: 573) Ac-Arg-c(hCys-D-Ala-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 574) Ac-Arg-c(hCys-Ala-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 575) Ac-Arg-c(hCys-Ala-D-Phe-Arg-Trp-Cys)-OH; (SEQ ID NO: 576) Ac-Arg-c(Cys-D-Ala-D-Phe-Arg-Trp-hCys)-NH2; (SEQ ID NO: 577) Ac-Arg-c(Pen-D-Ala-D-Phe-Arg-Trp-hCys)-NH2; (SEQ ID NO: 578) Ac-Arg-c(hCys-D-Ala-D-Phe(p-F)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 579) Ac-Arg-c(hCys-Pro-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 580) Ac-Nle-c(hCys-Pro-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 581) Arg-c(hCys-Pro-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 582) CH3-(CH2)4-CO-c(hCys-Pro-D-Phe-Arg-Trp-Cys)-NH2; and (SEQ ID NO: 583) Benzyl-CO-c(hCys-Pro-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In a further embodiment, the polypeptides of the present invention include the polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 584) Ac-Arg-c(Asp-D-Ala-D-Phe-Arg-Trp-Dbu)-NH2; (SEQ ID NO: 585) Ac-Arg-c(Glu-D-Ala-D-Phe-Arg-Trp-Dpr)-NH2; (SEQ ID NO: 586) Ac-Arg-c(Glu-Ala-D-Phe-Arg-Trp-Dpr)-NH2; (SEQ ID NO: 587) Ac-Arg-c(Dpr-D-Ala-D-Phe-Arg-Trp-Glu)-NH2; (SEQ ID NO: 588) Ac-Arg-c(Dpr-D-Ala-D-Phe(4-F)-Arg-Trp-Glu)-NH2; (SEQ ID NO: 589) Ac-Arg-c(Dpr-Ala-D-Phe-Arg-Trp-Glu)-NH2; (SEQ ID NO: 590) Ac-Arg-c(Dpr-Ala-D-Phe-Arg-Trp-Glu)-OH; (SEQ ID NO: 591) Ac-Nle-c(Dpr-Ala-D-Phe-Arg-Trp-Glu)-NH2; (SEQ ID NO: 592) Arg-c(Dpr-Ala-D-Phe-Arg-Trp-Glu)-NH2; (SEQ ID NO: 593) CH3-(CH2)4-CO-c(Dpr-Ala-D-Phe-Arg-Trp-Glu)-NH2; or Attorney Docket No.: R2054-7034WO (SEQ ID NO: 594) Benzyl-CO-c(Dpr-Ala-D-Phe-Arg-Trp-Glu)-NH2, or a pharmaceutically acceptable salt thereof. In yet another embodiment, the polypeptides of the present invention include a polypeptide represented by Formula (IV), wherein A4is an amino acid residue selected from Atc, Ala, QAla, Aib, Sar, Ser, Thr, Pro, Hyp, Asn, Gln, a substituted His, Trp, Tyr, Lys, Arg, sChp, or residue X. Examples of such peptides include peptides represented by any one of the following structural formulas: (SEQ ID NO: 595) Ac-Arg-c(Cys-D-Ala-His(3-Me)-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 596) Ac-Arg-c(Cys-D-Ala-His(1-Me)-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 568) Ac-Arg-c(Cys-D-Ala-Trp-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 567) Ac-Arg-c(Cys-D-Ala-Gln-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 566) Ac-Arg-c(Cys-D-Ala-Asn-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 597) Ac-Arg-c(Cys-D-Ala-Arg-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 598) Ac-Arg-c(Cys-D-Ala-Tyr-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 599) Ac-Arg- c(Cys-D-Ala-D-Pro-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 561) Ac-Arg-c(Cys-D-Ala-Pro-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 563) Ac-Arg-c(Cys-D-Ala-Pro-D-Phe(p-F)-Arg-Trp-Cys)-NH2; (SEQ ID NO: 600) Ac-Arg- c(Cys-D-Ala-Atc-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 601) Ac-Arg- c(Cys-D-Ala-QAla-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 602) Ac-Arg- c(Cys-D-Ala-sChp-D-Phe-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 603) Ac-Arg- c(Cys-D-Ala-X-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In example embodiments, the polypeptides of the present invention include a polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 574) Ac-Arg-c(hCys-Ala-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 573) Ac-Arg-c(hCys-D-Ala-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 604) Ac-Arg-c(hCys-D-Ala-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 585) Ac-Arg-c(Glu-D-Ala-D-Phe-Arg-Trp-Dpr)-NH2; (SEQ ID NO: 586) Ac-Arg-c(Glu-Ala-D-Phe-Arg-Trp-Dpr)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 605) Ac-Arg-c(hCys-Aib-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 606) Ac-Arg-c(hCys-Sar-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 607) Ac-Arg-c(hCys-Val-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 608) Ac-Arg-c(hCys-D-Val-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 609) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 610) Ac-Arg-c(hCys-D-Gln-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 611) Ac-Arg-c(hCys-Ala-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 612) Ac-Arg-c(D-Pen-D-Ala-D-Phe-Arg-Trp-hCys)-NH2; (SEQ ID NO: 576) Ac-Arg-c(Cys-D-Ala-D-Phe-Arg-Trp-hCys)-NH2; (SEQ ID NO: 613) Ac-Arg-c(Pen-D-Ala-D-Phe-Arg-Trp-hCys)-NH2; (SEQ ID NO: 614) Ac-Arg-c(D-hCys-D-Ala-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 579) Ac-Arg-c(hCys-Pro-D-Phe-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 615) Ac-Arg-c(hCys-D-Pro-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In another embodiment, the polypeptides of the present invention include polypeptides represented by Formula (IV), wherein A3is an amino acid residue selected from Tle, Val, Leu, Ile, Cha, Pro, Ser, Thr, Lys, Arg, His, Phe, Gln, Sar, Gly, Asn, or Aib; and A4is an amino acid residue selected from Atc, Ala, QAla, Aib, Sar, Ser, Thr, Pro, Hyp, Asn, Gln, a substituted His, Trp, Tyr, Lys, Arg, sChp, or residue X. Examples of such polypeptides are polypeptides represented by any one of the following structural formulas: (SEQ ID NO: 616) Ac-Arg-c(Cys-Val-Gln-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 570) Ac-Arg-c(Cys-D-Val-Gln-D-Phe-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 617) Ac-Arg-c(Cys-D-Val-His(1-Me)-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In a further embodiment, the polypeptides of the present invention include a polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 618) Ac-TzAla-c(Cys-Ala-Gln-D-Phe-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 619) Ac-Glu-c(Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. Attorney Docket No.: R2054-7034WO In yet another embodiment, the polypeptides of the present invention include a polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 596) Ac-Arg-c(Cys-D-Ala-His(1-Me)-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 567) Ac-Arg-c(Cys-D-Ala-Gln-D-Phe-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 566) Ac-Arg-c(Cys-D-Ala-Asn-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In a further embodiment, the polypeptides of the present invention include a polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 620) Ac-Arg-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 621) Ac-Arg-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 622) Ac-Arg-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 569) Ac-Arg-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In a further embodiment, the polypeptides of the present invention include a polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 623) Ac-Arg-c(Cys-D-Ala-His(1-Me)-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 624) Ac-Arg-c(Cys-D-Ala-Gln-D-2-Nal-Arg-Trp-Cys)-NH2; or (SEQ ID NO: 625) Ac-Arg-c(Cys-D-Ala-Asn-D-2-Nal-Arg-Trp-Cys)-NH2, or a pharmaceutically acceptable salt thereof. In a further embodiment, the polypeptides of the present invention include a polypeptide represented by any one of the following structural formulas: (SEQ ID NO: 626) Ac-Arg-c(Cys-D-Ala-His(1-Me)-D-Phe-Arg-Trp-Cys)-OH; (SEQ ID NO: 627) Ac-Arg-c(Cys-D-Ala-Gln-D-Phe-Arg-Trp-Cys)-OH; or (SEQ ID NO: 628) Ac-Arg-c(Cys-D-Ala-Asn-D-Phe-Arg-Trp-Cys)-OH, or a pharmaceutically acceptable salt thereof. In one example embodiment, an MC4R agonist is a compound represented by Formula (X): Attorney Docket No.: R2054-7034WO or a pharmaceutically chemical substituents are defined as follows: R1is –NH-C(O)- or –C(O)-NH-; R2 is –H, –CH2-, or, R2 , together with R3, forms a pyrrolidine ring optionally substituted with –OH; R3is –(CH2)2- if R2is –CH2-, and otherwise R3is selected from ; R4a, R4b, and R4care each independently selected from hydrogen, halo, (C1-C10)alkyl- halo, (C1-C10)alkyl-dihalo, (C1-C10)alkyl-trihalo, (C1-C10)alkyl, (C1-C10)alkoxy, (C1- Attorney Docket No.: R2054-7034WO C10)alkylthio, aryl, aryloxy, nitro, nitrile, sulfonamide, amino, hydroxyl, carboxy, and alkoxy- carbonyl. In one example embodiment, R4a, R4b, and R4cis not hydrogen. R5is –OH or –N(R6a)(R6b); R6aand R6bare each independently H or C1 to C4 linear, branched or cyclic alkyl chain; R7is –H or –C(O)-NH2; w is in each instance independently 0 to 5; x is 1 to 5; y is 1 to 5; z is in each instance independently 1 to 5. An example of a compound of Formula (X) is a cyclic peptide defined by Formula (XI): (XI), or a pharmaceutically acceptable salt thereof. one the MC4R agonist is Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg- Trp-Cys)-NH2 (SEQ ID NO: 140) or a pharmaceutically acceptable salt thereof. In another example embodiment, the MC4R agonist is Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe- Arg-Trp-Cys)-NH2 (SEQ ID NO: 148) or a pharmaceutically acceptable salt thereof. In some embodiments, the MC4R agonist is an agonist described in WO2014 / 144260 A1, incorporated herein by reference. In one example embodiment, the MC4 agonist is a compound represented by Formula (XII): A1-Yyy-c(Aaa-Xxx-D-Phe-Arg-Trp-Bbb)-A2(XII) Aaa and Bbb are selected from Cys, hCys, Pen capable of establishing a disulfide bridge; or Glu, Asp, Lys, Orn, Dpr, Dbu capable of establishing a lactam bridge; Attorney Docket No.: R2054-7034WO Xxx is Asn, Gln, Ser, Thr; Yyy is Lys, Arg, D-Lys, D-Arg; A1 is H, Ac; A2 is OH, NH2; In embodiments, the MC4R agonist is chosen from one or more of the following compounds, (or pharmaceutically acceptable salt thereof): (SEQ ID NO: 629) Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 630) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 631) Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 632) Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 633) Ac-Arg-c(Glu-Gln-D-Phe-Arg-Trp-Dpr)-NH2; (SEQ ID NO: 634) Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 635) H-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 636) H-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 637) Ac-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 638) H-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 639) Ac-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 640) H-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 641) Ac-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 642) Ac-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 643) H-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 644) H-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 645) Ac-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 646) H-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 647) Ac-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 648) H-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 649) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 650) H-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 651) H-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 652) Ac-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 653) H-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 654) Ac-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 655) H-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 656) Ac-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 657) Ac-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 658) H-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 659) H-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 660) Ac-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 661) H-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 662) Ac-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 663) H-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 664) Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 665) H-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 666) H-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 667) Ac-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 668) H-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 669) Ac-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 670) H-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 671) Ac-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 672) Ac-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 673) H-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 674) H-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 675) Ac-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 676) H-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 677) Ac-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 678) H-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 679) Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 680) H-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 681) H-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 682) Ac-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 683) H-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 684) Ac-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 685) H-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 686) Ac-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 687) Ac-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 688) H-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 689) H-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 690) Ac-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 691) H-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 692) Ac-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2, or (SEQ ID NO: 693) H-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2. In some embodiments, the MC4R agonist is a compound of Formula (XII-a): H-Yyy-c(Aaa-Xxx-D-Phe-Arg-Trp-Bbb)-NH2 (XII-a) or a pharmaceutically acceptable salt thereof, wherein: Aaa and Bbb are selected from Cys, hCys, Pen capable of establishing a disulfide bridge; or Glu, Asp, Lys, Orn, Dpr, Dbu capable of establishing a lactam bridge; Xxx is Asn, Gln, Ser, Thr; and Yyy is Lys, Arg, D-Lys, D-Arg. In some embodiments, the compound of Formula (XII-a) is selected from: (SEQ ID NO: 635) H-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 643) H-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 646) H-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 650) H-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 653) H-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 658) H-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 661) H-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 665) H-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 668) H-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 673) H-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 676) H-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 680) H-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 683) H-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 688) H-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 691) H-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; and (SEQ ID NO: 693) H-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2. In some embodiments, the MC4R agonist is a compound of Formula (XII-b): Ac-Yyy-c(Aaa-Xxx-D-Phe-Arg-Trp-Bbb)-NH2 (XII-b) or a pharmaceutically acceptable salt thereof, wherein: Aaa and Bbb are selected from Cys, hCys, Pen capable of establishing a disulfide bridge; or Glu, Asp, Lys, Orn, Dpr, Dbu capable of establishing a lactam bridge; Xxx is Asn, Gln, Ser, Thr; and Yyy is Lys, Arg, D-Lys, D-Arg. In some embodiments, the compound of Formula (XII-b) is selected from: (SEQ ID NO: 629) Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 630) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 631) Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 632) Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 633) Ac-Arg-c(Glu-Gln-D-Phe-Arg-Trp-Dpr)-NH2; (SEQ ID NO: 637) Ac-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 641) Ac-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 645) Ac-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 652) Ac-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 656) Ac-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 660) Ac-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 667) Ac-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 671) Ac-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 675) Ac-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 682) Ac-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 686) Ac-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 690) Ac-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; and (SEQ ID NO: 692) Ac-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2. In some embodiments, the MC4R agonist is a compound of Formula (XII-c): A1-Yyy-c(Aaa-Xxx-D-Phe-Arg-Trp-Bbb)-A2(XII-c) Attorney Docket No.: R2054-7034WO or a pharmaceutically acceptable salt thereof, wherein: A1 is H or Ac; A2is OH or NH2; Yyy is L-Arg or D-Arg; Aaa and Bbb are selected from Cys, hCys, and Pen capable of establishing a disulfide bridge; or Glu, Asp, Lys, Orn, Dpr, and Dbu capable of establishing a lactam bridge; and Xxx is Asn, Gln, Ser, or Thr. In some embodiments, the compound of Formula (XII-c) is selected from: (SEQ ID NO: 629) Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 630) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 631) Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 632) Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 633) Ac-Arg-c(Glu-Gln-D-Phe-Arg-Trp-Dpr)-NH2; (SEQ ID NO: 634) Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 635) H-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 636) H-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 637) Ac-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 638) H-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 639) Ac-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 640) H-D-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 649) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 650) H-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 651) H-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 652) Ac-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 653) H-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 654) Ac-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 655) H-D-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 664) Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 665) H-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 666) H-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 667) Ac-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 668) H-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 669) Ac-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 670) H-D-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 679) Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 680) H-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 681) H-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 682) Ac-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 683) H-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 684) Ac-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; and (SEQ ID NO: 685) H-D-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH. In some embodiments, the MC4R agonist is a compound of Formula (XII-d): A1-Yyy-c(Aaa-Xxx-D-Phe-Arg-Trp-Bbb)-A2 (XII-d) or a pharmaceutically acceptable salt thereof, wherein: A1 is H or Ac; A2 is OH or NH2; Yyy is L-Lys or D-Lys; Aaa and Bbb are selected from Cys, hCys, and Pen capable of establishing a disulfide bridge; or Glu, Asp, Lys, Orn, Dpr, and Dbu capable of establishing a lactam bridge; and Xxx is Asn, Gln, Ser, or Thr. In some embodiments, the compound of Formula (XII-d) is selected from: (SEQ ID NO: 641) Ac-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 642) Ac-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 643) H-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 644) H-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 645) Ac-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 646) H-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 647) Ac-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 648) H-D-Lys-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 656) Ac-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 657) Ac-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 658) H-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 659) H-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 660) Ac-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 661) H-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 662) Ac-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 663) H-D-Lys-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 671) Ac-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 672) Ac-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 673) H-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 674) H-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 675) Ac-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 676) H-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 677) Ac-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 678) H-D-Lys-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 686) Ac-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 687) Ac-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 688) H-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 689) H-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 690) Ac-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 691) H-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 692) Ac-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2, and (SEQ ID NO: 693) H-D-Lys-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2. In some embodiments, the MC4R agonist is an agonist described in WO2014 / 144260 or WO2017 / 059075, each of which is incorporated herein by reference. Administration of a compound or pharmaceutically acceptable salt thereof or a composition comprising a compound or pharmaceutical salt of a compound of the disclosure useful to practice the methods described herein, can be continuous, hourly, four times daily, three time daily, twice daily, once daily, once every other day, twice weekly, once weekly, once every two weeks, once a month, or once every two months, or longer or some other intermittent dosing regimen. Examples of administration of a compound or composition comprising a compound or pharmaceutical salt of a compound of the disclosure include peripheral Attorney Docket No.: R2054-7034WO administration. Examples of peripheral administration include oral, subcutaneous, intraperitoneal, intramuscular, intravenous, rectal, transdermal or intranasal forms of administration. As used herein, peripheral administration can include all forms of administration of a compound or a composition comprising a compound of the instant disclosure which excludes intracranial administration. Examples of peripheral administration include, but are not limited to, oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous or subcutaneous injection, extended release, slow release implant, depot and the like), nasal, vaginal, rectal, sublingual or topical routes of administration, including transdermal patch applications and the like. The nomenclature used to define the peptides is that typically used in the art wherein the amino group at the N-terminus appears to the left and the carboxyl group at the C-terminus appears to the right. Where the amino acid has D and L isomeric forms, it is the L form of the amino acid that is represented unless otherwise explicitly indicated. The compounds of the disclosure useful for practicing the methods described herein may possess one or more chiral centers and so exist in a number of stereoisomeric forms. All stereoisomers and mixtures thereof are included in the scope of the present disclosure. Racemic compounds may either be separated using preparative HPLC and a column with a chiral stationary phase or resolved to yield individual enantiomers utilizing methods known to those skilled in the art. In addition, chiral intermediate compounds may be resolved and used to prepare chiral compounds of the disclosure. The compounds described herein may exist in one or more tautomeric forms. All tautomers and mixtures thereof are included in the scope of the present disclosure. For example, a claim to 2-hydroxypyridinyl would also cover its tautomeric form, α-pyridonyl. The present disclosure further features providing an MC4R agonist in combination with an additional agent. Exemplary agents include a second MC4R agonist (e.g., an agent described herein or elsewhere), or an agent aimed to treat a symptom of obesity or a co-morbidity. For example, the additional agent may be an anti-hypertensive drug, a pain medication, an anti- inflammatory, a lipid-lowering agent, a cardiovascular drug, or a diuretic. The combination therapy may be administered as a single formulation or as separate formulations. In an embodiment, the MC4R agonist and the additional agent are administered as a single pharmaceutical composition. In an embodiment, the MC4R agonist and the additional agent are Attorney Docket No.: R2054-7034WO administered as separate pharmaceutical compositions. In the case of separate formulations, the MC4R agonist and the additional agent may be administered concomitantly or sequentially. In an embodiment, the MC4R agonist and the additional agent are administered concomitantly. In an embodiment, the MC4R agonist and the additional agent are administered sequentially. For example, the MC4R agonist may be administered prior to the additional agent or subsequent to the additional agent. In some embodiments, the administration of the MC4R agonist and the additional agent has a synergistic or additive effect. For example, the administration of the MC4R agonist and the additional agent may have an additive effect, in which the therapeutic effect of the MC4R agonist and the additional agent is the total sum of the effects of each of the components individually. In contrast, the administration of the MC4R agonist and the additional agent may have a synergistic effect, in which the therapeutic effect of the MC4R agonist and the additional agent is greater than the sum of the individual components. The synergistic effect of the combination of the MC4R agonist and the additional agent may be 0.1%, 0.25%.0.5%.0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%.90%.95%, or more than the total sum of the effects of the MC4R agonist and the additional agent administered individually. In an embodiment, the synergistic effect of the combination of the MC4R agonist and the additional agent is greater than between 5% and 75% of the total sum of the effects of the MC4R agonist and the additional agent administered individually. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Also, all publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. Potassium Channel Activator Compounds The present disclosure further features combinations of an MC4R agonist with a potassium channel activator compound (e.g., a SURx / Kirxchannel activator compound) an aspect, the present disclosure relates to methods of treatment comprising a SURx / Kirx channel activator. Attorney Docket No.: R2054-7034WO The KATP channel Kir.6 / SUR1 is a multimeric ATP-driven ion channel which mediates cell membrane potential in pancreatic β-cells. The ATP-driven ion channel comprises a sulphonyl urea receptor SUR1 capable of binding to glucose, sulphonyl urea, diazoxide and other SURx / Kirxchannel activator compounds, initiating a depolarization of the cell membrane, Ca2+transport, and ultimately exocytosis of secretory vesicles containing insulin, thereby modulating blood glucose levels. See Reimann, F. Br. J. Pharmacol.2001: 132, 1542-1548. In an embodiment, the SURx / Kirxchannel activator compound has the structure of Formula (XIII): R5Rxor a stereoisomer, hydrate, or isotope thereof, wherein A is C(R’); each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; each of R1, R2, R5, and R6are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rx is hydrogen or wherein A and D form a double bond and Ryis hydrogen; R3is C1-C6 alkyl, C2- C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4; R’ is absent, hydrogen, or C1-C6 alkyl; each R4is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl Attorney Docket No.: R2054-7034WO optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano. In an embodiment, B is N. In an embodiment, D is N. In an embodiment, A is C. In an embodiment, R5 is hydrogen. In an embodiment, R6 is hydrogen. In an embodiment, each of R1 and R2is independently hydrogen, fluorine, chlorine, bromine, iodine, nitro, or cyano. In an embodiment, R1is hydrogen, fluorine, chlorine, bromine, iodine, nitro, or cyano. In an embodiment, R1 is hydrogen, fluorine, chlorine, bromine, iodine, cyano. In an embodiment, R1 is hydrogen, fluorine or chlorine. In an embodiment, R1is hydrogen. In an embodiment, R1is fluorine. In an embodiment, R1is chlorine. In an embodiment, R1is bromine. In an embodiment, R1 is iodine. In an embodiment, R1 is cyano. In an embodiment, R2 is hydrogen, fluorine, chlorine, bromine, iodine, nitro, or cyano. In an embodiment, R2 is hydrogen, fluorine, chlorine, bromine, iodine, cyano. In an embodiment, R2is hydrogen, fluorine or chlorine. In an embodiment, R2 is hydrogen. In an embodiment, R2 is fluorine. In an embodiment, R2 is chlorine. In an embodiment, R2 is bromine. In an embodiment, R1 is iodine. In an embodiment, R2is cyano. In an embodiment, R3is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), each of which is optionally substituted with optionally substituted with one or more R7.In an embodiment, R3is C1-C6 heteroalkyl optionally substituted with optionally substituted with one or more R7.In an embodiment, R3is C1-C6 haloalkyl, optionally substituted with optionally substituted with one or more R7. In an embodiment, R3is cycloalkyl, optionally substituted with optionally substituted with one or more R7.In an embodiment, R3heterocyclyl, optionally substituted with optionally substituted with one or more R7. In an embodiment, R3 is N(RB)(RC). In an embodiment, RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7(e.g., a 4-membered heterocyclyl, 5-membered heterocyclyl, 6-membered heterocyclyl, or a bridged heterocyclyl). In an embodiment, RBis hydrogen. In an embodiment, RCis C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, each optionally substituted with one or more R7. In an embodiment, RCis C1-C6 alkyl optionally substituted with one or more R7. In an embodiment, RCis C1-C6 heteroalkyl optionally substituted with one Attorney Docket No.: R2054-7034WO or more R7. In an embodiment, RCis C1-C6 haloalkyl optionally substituted with one or more R7. In an embodiment, RCis cycloalkyl optionally substituted with one or more R7 (e.g., monocyclic cycloalkyl, bicyclic cycloalkyl). In an embodiment, RCis cycloalkyl substituted with one or more R7, wherein R7 is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano. In an embodiment, RCis heterocyclyl optionally substituted with one or more R7. In an embodiment, the compound of Formula (XIII) is not 3-(tert-butylamino)-7-chloro- 4H-benzo[e][1,2,4]thiadiazine 1,1-dioxide or a pharmaceutically acceptable salt thereof. In an embodiment, the compound of Formula (XIII) is 3-(tert-butylamino)-7-chloro-4H- benzo[e][1,2,4]thiadiazine 1,1-dioxide or a pharmaceutically acceptable salt thereof. In an embodiment, the compound of Formula (XIII) is diazoxide. In an embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-a): RxH R3Ry(XIII-a) or a pharmaceutically hydrate, or isotope thereof, wherein A is C; each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; R1 and R2 are hydrogen, fluorine, chlorine, bromine and iodine; and wherein A and B form a double bond and Rxis H or wherein A and D form a double bond and Ryis H; R3is independently selected from the group consisting of: H H H H N N N NCH2F ,

[0002] Attorney Docket No.: R2054-7034WO H H H N N N C H H CH N C2C H O , one to two substituents selected from the group consisting of fluoro and hydroxy, ethynyl, C1-C2 alkoxy, (methoxy)-C1-C2 alkyl, cyano, fluoro, (methylsulfonyl)-C1-C2 alkyl, (dimethylamino)-C1-C2 alkyl and n-methyl carbamoyl, under the proviso that said compound is not 3-(tert-butylamino)- 7-chloro-4H-benzo[e][1,2,4]thiadiazine 1,1-dioxide.In relation to these compounds the present inventors have surprisingly found that these compounds exhibit remarkable potency for binding selectively to SURx / Kirxand inhibiting glucose stimulated insulin secretion. In view of the fact that the binding of these compounds to the target is so specific, reduced off target effects are observed. Moreover, the compounds according to the present invention exhibit excellent bioavailability, stability and safety and can be administered orally. In another embodiment, the compound of Formula (XIIII) is a compound of Formula (XIII-b): Attorney Docket No.: R2054-7034WO R5Rx RBD N (XIII-b) or a stereoisomer, hydrate, or isotope thereof, wherein A, B, D, R1, R2, R5, R6, Rx Ry, RA,RB, RC, and R7are defined as provided for Formula (XIII). In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-c): R5RxRBc) or a hydrate, or isotope thereof, wherein A, B, D, R1, R2, R5, R6, Rx Ry, RA,RB, RC, and R7are defined as provided for Formula (XIII), m is an integer between 0 and 12; and n is an integer between 0 and 4. In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-d): Rx RBd) or a hydrate, or isotope thereof, wherein R1, R2, R5, Rx, and R7are defined as provided for Formula (XIII), m is an integer between 0 and 12; and n is an integer between 0 and 4. Attorney Docket No.: R2054-7034WO In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-e): RxRBe) or a hydrate, or isotope thereof, are as (XIII), m is an integer between 0 and 12; and n is an integer between 0 and 4. In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-f): RxRBm(XIII-f) or a hydrate, or isotope thereof, wherein R1, R5, Rx, and R7are defined as provided for Formula (XIII), m is an integer between 0 and 12; and n is an integer between 0 and 4. In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-g): m (XIII-g) Attorney Docket No.: R2054-7034WO or a pharmaceutically acceptable salt, tautomer, stereoisomer, hydrate, or isotope thereof, wherein R1, R2, R5, Rx, and R7are defined as provided for Formula (XIII), m is an integer between 0 and 12; and n is an integer between 0 and 4. In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-h): RxRBor a hydrate, or isotope thereof, as for Formula (XIII). In another embodiment, the compound of Formula (XIII) is a compound of Formula (XIII-d): RxRBd) or a hydrate, or isotope thereof, wherein R1, R2, R5, RB, Rx, and R7are defined as provided for Formula (XIII), m is an integer between 0 and 12; and n is an integer between 0 and 4. In an embodiment, the compounds of Formula (XIII) described herein exhibit improved properties over the compounds in the art. The known compounds cause serious side effects due to lack of channel specificity. Moreover, the benefit for the patient group at large of compounds already known in the prior art is modest as the responsiveness of patients suffering from HI, in particularly CHI varies considerably within patients. It is assumed that this is due to their low specificity. In view of the high specificity of the compounds of the present invention responsiveness of patients suffering from HI, in particular CHI will be considerably better. Attorney Docket No.: R2054-7034WO With respect to the compounds according to the present invention it is noted that they include all their acid addition and base salts, tautomeric forms, metabolites or prodrugs. The present invention further includes unsolvated forms, solvated forms including hydrated forms of the compounds of the present invention. Preferred compounds according to the present invention are wherein said compounds are according to general formula (XIII) such that: - A is carbon (C); - B and D are Nitrogen (N); and - wherein A and B or A and D are connected via a double or single bond; and - wherein R1and R2are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine and iodine; and - wherein A and B form a double bond and Rx is H or wherein A and D form a double bond and Ryis H; and - wherein R3is independently selected from the group consisting of: H H H H N N N R4N CF3CH CHH2CCH2F ,

[0003] Attorney Docket No.: R2054-7034WO H H22C C H H N N H H the structure of Formula (XIV): R5Rxor a pharmaceutically or isotope thereof, wherein: A is C(R’); each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; X is C(R’) or S; when X is C (R’) then Y is C(R’); or, when X is S, then Y is absent; each of R1, R2, R5, and R6 are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rxis hydrogen or wherein A and D form a double bond and Ry is hydrogen; R3 is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4; Attorney Docket No.: R2054-7034WO R’ is absent, hydrogen, or C1-C6 alkyl; each R4 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano. In some embodiments, the SURx / Kirx channel activator compound is a compound disclosed in WO1997049692A1, WO2002074945A1, WO2003087089A1, WO2003091245A1, WO2005063742A2, WO2006045799A2, WO2007125048A1, WO2010093243A1, WO2013130411A1, WO2014046172A1, WO2019084271A1, WO2021236818A1, WO2004087053A2, WO2005058348A1, WO2007053514A2, WO2007081521A2, WO2007136125A1, WO2009006483A1, WO2017098421A1, US20100226943A1, WO2000037474A1, WO2001002410A1, WO2002000222A1, WO2002000665A1, WO2002050085A1, WO2003045954A1, WO2003045955A1, WO2003105896A1, WO2004005299A1, WO2005013962A1, WO2006045799A2, WO2006088798A2, WO2007020286A2, WO2007125048A1, WO2009000038A1, WO2022125784A1, WO1997026265A1, WO2003087089A1, WO1999003861A1, or WO1999032494A1, the contents of which are hereby incorporated by reference in their entirety. In some embodiments, the SURx / Kirx channel activator compound is a compound disclosed in US4035374A, US20070254862A1, DE2757922A1, DE2757999A1, EP105732A2, EP112142A2, EP172968A1, EP355612A2, JP6284823B2, JP51054576A, JP60072868A, EP386931A1, JP2015214525A, JP2016011275A, JP3254698A, Attorney Docket No.: R2054-7034WO JP60112781A, DK200400395A, or EP1676573A1, the contents which are hereby incorporated by reference in their entirety. In an aspect, the SURx / Kirx channel activator compound is diazoxide, which is disclosed in US2986573A, the contents of which is hereby incorporated by reference in its entirety. In an aspect, the SURx / Kirx channel activator compound is a compound disclosed in DE2757999A1, e.g., the SURx / Kirx channel activator compound is a compound of formula (XV): OOS R2R N , wherein: R represents hydrogen, alkoxyalkyl, alkylthio, alkylcarbonyl, phenylcarbonyl, phenylsulfonyl, phenylsulfinyl, phenyloxy, phenylthio, where the phenyl radicals can be substituted by alkyl, alkoxy, halogen, nitro or amino, or for thenoyl or pyridylcarbonyl, which can be substituted by alkyl; R1is hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, alkoxyalkyl, alkylthio, alkylcarbonyl, phenylcarbonyl, phenylsulfonyl, phenylsulfinyl, phenyloxy or phenylthio, the phenyl radicals being represented by alkyl, alkoxy , halogen, nitro or amino can be substituted, or stands for thenoyl or pyridylcarbonyl, whereby these can be substituted by alkyl; R2stands for hydrogen or alkyl; R3stands for hydrogen or alkyl; R4stands for the NH2, NHR5or the NR5R6- Group, where the radicals R5and R6can be identical or different and are alkyl or phenyl or phenylalkyl, and in the case of v on R5- alkyl this group can be connected to a carbon atom of the alkylene group to form a 5- or 6- membered ring, or where the radicals R5and R6together with the nitrogen atom can form an optionally substituted azabicycloalkyl radical with 6 to 10 ring members or R represents a cycloalkyleneimino group optionally interrupted by O, S, NH or NR5and / or substituted by one or two alkyl groups with a total of 5 to 7 ring members and in which the ring can optionally contain one, two or three double bonds, and alkylene represents a divalent Attorney Docket No.: R2054-7034WO alkylene group, which can optionally be substituted by alkyl and / or by a hydroxy, acyloxy or alkoxy group, and their physiologically compatible salts. In an aspect, the SURx / Kirx channel activator compound is a compound disclosed in WO2000037474A1, e.g., the SURx / Kirx channel activator compound is a compound of formula (XVI): Y H H R1N N , wherein X and Y independently are C1-6-alkyl or C1-6-alkoxy; R1, R2and R3independently are C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, carboxy, C1-6-alkoxycarbonyl or aryl, all of which are optionally being mono- or polysubstituted with halogen, hydroxy, oxo, or aryl; or R1is as defined above and R2-C-R3form a C3-6 -cyeloalkyl group, optionally being mono- or polysubstituted with C1-6-alkyl, perhalomethyl, halogen, hydroxy or aryl; or -CR1R2R3form a 4- to 12-membered bicyclic or tricyclic carbocyciic system, optionally being mono- or polysubstituted with C.-6-alkyl, perhalomethyl, halogen, hydroxy or aryl; or a salt thereof with a pharmaceutically acceptable acid or base including all optical isomers of compounds of formula I, some of which are optically active, and also their mixtures including racemic mixtures, or any tautomeric form thereof. In some embodiments, the SURx / Kirx channel activator compound is a compound as shown in the Table 2 below: Compound Name No. 77 3-tert-butylamino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 78 6-Chloro-3-(1,1-dimethylpropylamino)-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 79 6-Chloro-3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 80 6-Chloro-3-(2-hydroxy-1,1-dimethylethylamino)-4H-thieno[3,2-e]-1,2,4- thiadiazine 1,1-dioxide 81 6-Chloro-3-(1,1,3,3-tetramethylbutylamino)-4H-thieno[3,2-e]-1,2,4- thiadiazine 1,1-dioxide 82 3-(1-adamantyl)amino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1 - dioxide Attorney Docket No.: R2054-7034WO 83 1-(6-Chloro-1 ,4-dihydro-1,1-dioxo-thieno[3,2-e]-1λ6,2,4-thiadiazin-3- ylamino)-cyclopropanecarboxylic acid ethyl ester 84 6-Chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4- thiadiazine 1,1-dioxide 85 6-Chloro-3-(1-hydroxymethylcyclopentyl)amino-4H-thieno[3,2-e]-1,2,4- thiadiazine 1,1-dioxide 86 1-(6-Chloro-1,4-dihydro-1,1-dioxo-thieno[3,2-e]-1λ6,2,4-thiadiazin-3- ylamino)-cyclopropanecarboxylic acid 87 6-Chloro-3-(1-methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 88 6-Chloro-3-(1-methylcyclohexyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1 -dioxide 89 6-Chloro-3-(1-methylcyclopentyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 90 6-Chloro-3-(1-ethylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1- dioxide Exemplary SURx / Kirx channel activator compound compounds of the present disclosure are shown in Table 3 below: Compound Structure Name No. SURx / Kirx H N 7-chloro-3-methyl-4H-1,2,4- channel benzothiadiazine 1,1-dioxide activator N compound I Cl S OOSURx / Kirx H H N 6-chloro-3-[[11- channel N methylcycloproyl]amino]-4H- activator Cl S N thieno[3,2-e]-1,2,4-thiadiazine 1,1- compound II S OOdioxide 1HH N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-fluoro-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide 2HH N 7-fluoro-3-((1- N methylcyclobutyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide Attorney Docket No.: R2054-7034WO H H N 7-fluoro-3-((3- N fluorobicyclo[1.1.1]pentan-1- N F yl)amino)-4H- F S OObenzo[e][1,2,4]thiadiazine 1,1- dioxide H H N 3-(bicyclo[2.1.1]hexan-1-ylamino)- N 7-fluoro-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N 3-((2,2-dimethylcyclopropyl)amino)- 7-fluoro-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N (S*)-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide H H N N (R*)-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide H H N N 7-fluoro-3-(spiro[2.2]pentan-1- ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N (S*)-7-fluoro-3-(spiro[2.2]pentan-1- ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N (R*)-7-fluoro-3-(spiro[2.2]pentan-1- ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N 7-fluoro-3-(spiro[2.3]hexan-1- ylamino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 3-((1-ethylcyclopropyl)amino)-7- N fluoro-4H-benzo[e][1,2,4]thiadiazine F S 1,1-dioxide OO Attorney Docket No.: R2054-7034WO H H 3-([1,1’-bi(cyclopropan)]-1- N N ylamino)-7-fluoro-4H- benzo[e][1,2,4]thiadiazine 1,1- N F S dioxide OOClHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-chloro-7-fluoro-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide) H Hl6-ch NNloro-7-fluoro-3- (spiro[2.3]hexan-1-ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H HlN(S*)-6-chloro-7-fluoro-3- N (spiro[2.3]hexan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H Hl(R*)-6-chloro-7-fluoro-3- NN(spiro[2.3]hexan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H HlN6-chloro-7-fluoro-3-((3- N methylbicyclo[1.1.1]pentan-1- N yl)amino)-4H- F S OObenzo[e][1,2,4]thiadiazine 1,1- dioxide H H 6-chloro-7-fluoro-3-((3- NNfluorobicyclo[1.1.1]pentan-1- N yl)amino)-4H- S F OObenzo[e][1,2,4]thiadiazine 1,1- dioxide lHN H N 6-chloro-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide lHN H N (S*)-6-chloro-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide lHN H N (R*)-6-chloro-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide Attorney Docket No.: R2054-7034WO lHH NN CF36-chloro-7-fluoro-3-((1- (trifluoromethyl)cyclopropyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide lHH N 6-chloro-7-fluoro-3-((1- N methylcyclobutyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide lHH NN(rac)-trans-6-chloro-7-fluoro-3-((2- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide lHH NN6-chloro-7-fluoro-3-(((1S*,2S*)-2- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]-thiadiazine 1,1- OOdioxide lHH NN6-chloro-7-fluoro-3-(((1R*,2R*)-2- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]-thiadiazine 1,1- OOdioxide H lHNN6-chloro-7-fluoro-3- (spiro[2.2]pentan-1-ylamino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H Hl(S*)-6-chloro-7-fl NNuoro-3- (spiro[2.2]pentan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H HlNN(R*)-6-chloro-7-fluoro-3- (spiro[2.2]pentan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H H l NN3-(bicyclo[2.1.1]hexan-1-ylamino)- 6-chloro-7-fluoro-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide FHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6,7-difluoro-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide Attorney Docket No.: R2054-7034WOFHH 6,7-difluoro-3-(spiro[2.3]he NNxan-1- ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide FHH N 6,7-difluoro-3-((1- N methylcyclobutyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H FNN 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-chloro-6-fluoro-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-chloro-8-fluoro-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- FO Odioxide H BrHNN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-bromo-4H-benzo[e]- N S [1,2,4]thiadiazine 1,1-dioxide OOH H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 8-bromo-4H- N S benzo[e][1,2,4]thiadiazine 1,1- BrO Odioxide IHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-iodo-4H-benzo[e][1,2,4]thiadiazine N S 1,1-dioxide OOH H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-methyl-4H- N S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide NCHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 4H-benzo[e][1,2,4]-thiadiazine-6- N S carbonitrile 1,1-dioxide OOH H N N 3-(tert-butylamino)-7-fluoro-4H- benzo[e][1,2,4]thiadiazine 1,1- N F S dioxide OO Attorney Docket No.: R2054-7034WO H H N N 3-((1,3-difluoropropan-2-yl)amino)- F 7-fluoro-4H- F N SFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1-(dimethylamino)-2- N methylpropan-2-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N O 7-fluoro-3-((4-methoxy-2- methylbutan-2-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- F (fluoromethyl)cyclopropyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N O 7-chloro-3-((4-methoxy-2- methylbutan-2-yl)amino)-4H- N l S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1,3-difluoropropan-2- F yl)amino)-4H- ClN SFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1-(dimethylamino)-2- N methylpropan-2-yl)amino)-4H- N l S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- methylcyclopropyl)amino)-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- F (fluoromethyl)cyclopropyl)amino)- N Cl S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((3,3- F difluorocyclobutyl)amino)-4H- NClSFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide Attorney Docket No.: R2054-7034WO H H Cl N N 3-(tert-butylamino)-6-chloro-7- fluoro-4H-benzo[e][1,2,4]thiadiazine N F S 1,1-dioxide OOH H Cl N N 6-chloro-3-((1,3-difluoropropan-2- F yl)amino)-7-fluoro-4H- F N SFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-3-((1-(dimethylamino)-2- N methylpropan-2-yl)amino)-7-fluoro- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H l N N O 6-chloro-7-fluoro-3-((4-methoxy-2- methylbutan-2-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-3-((1- ethynylcyclopropyl)amino)-7-fluoro- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- F (fluoromethyl)cyclopropyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-3-((3,3- F difluorocyclobutyl)amino)-7-fluoro- F N SF4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-chloro-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H 7-fluoro-3-((1- N N isopropylcyclopropyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide Attorney Docket No.: R2054-7034WO H H Cl N N 6-chloro-7-fluoro-3-((1- isopropylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- O (methoxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- OH (hydroxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- O (methoxymethyl)cyclobutyl)amino)- N Cl S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- OH (hydroxymethyl)cyclobutyl)amino)- N Cl S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- O (methoxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- OH (hydroxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N (R)-7-fluoro-3-((tetrahydrofuran-3- O yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N (R)-7-chloro-3-((tetrahydrofuran-3- O yl)amino)-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N (R)-6-chloro-7-fluoro-3- O ((tetrahydrofuran-3-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide Attorney Docket No.: R2054-7034WO 74 H NN(R)-7-fluoro-3-(2- (hydroxymethyl)azetidin-1-yl)-4H- N OH benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide 75 H NN(R)-7-chloro-3-(2- (hydroxymethyl)azetidin-1-yl)-4H- N OH benzo[e][1,2,4]thiadiazine 1,1- Cl S OOdioxide 76 H ClN N(R)-6-chloro-7-fluoro-3-(2- OH (hydroxymethyl)azetidin-1-yl)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide Methods of Use Disclosed herein are methods for treating and / or preventing a disease, disorder or condition with a combination of a potassium channel activator (e.g., a SURx / Kirx channel activator compound) and an MC4R agonist. Exemplary diseases or disorders may include obesity or an obesity-related disorder, a metabolic disorder (e.g., hyperphagia, congenital hyperinsulinism), cancer, a neurological disorder, a cardiovascular disorder, a pulmonary disorder, an integumentary disorder, a sexual disorder, a urinary disorder, or a symptom thereof. In some embodiments, the disease, disorder or condition is a metabolic disorder. In some embodiments, the metabolic disorder is hyperinsulinism (HI), congenital hyperinsulinism (CHI), persistent hyperinsulinism, or transient hyperinsulinism. In some embodiments, the metabolic disorder is a hyperinsulism-related syndrome, e.g., Beckwith-Wiedemann syndrome, hyperinsulinism-hyperammonaemia (HIHA) syndrome, Sotos syndrome, Turner syndrome, Costello syndrome, Kabuki syndrome, and the like. Glucose is an important source of energy for mammals, as it is transported from the intestines or liver to body cells via the bloodstream and is made available for cellular metabolism by secretion of the hormone insulin. By means of a delicate mechanism, referred to as glucose homeostasis, the body in healthy human subjects is able to maintain the glucose concentration within a preferred range of around 3.5 to 5.5 mmol / L. Blood glucose levels outside this normal range may be an indicator of a medical condition. Attorney Docket No.: R2054-7034WO The major hormones involved in regulation of glucose metabolism over the time scale of hours are insulin and glucagon. Insulin and glucagon are secreted by the pancreatic islets and are both secreted in response to blood glucose levels, but in opposite fashion. Insulin is an important peptide hormone involved in nutrient homeostasis which is produced by the β-cells in the pancreatic islets. It regulates the metabolism of carbohydrates and fats by promoting the transport of glucose from the blood to skeletal muscles and fat tissue. The general stimulus for insulin secretion is a high blood glucose. Although there is always a low level of insulin secreted by the pancreas, the amount secreted into the blood increases as the blood glucose rises. On the other hand, when glucose levels are low, glucagon secretion increases and insulin secretion decreases. The most important effect of the glucagon increase is that it triggers the liver to release the glucose it has stored in its cells (as the polymer glycogen) into the bloodstream. The net effect of this release of glucose is the raising of the blood glucose concentration. Moreover, glucagon also induces the liver and other cells to make glucose out of building blocks obtained from other nutrients found in the body (e.g., protein). Blood glucose levels outside the normal range may be an indicator of a medical condition. A persistently high level is referred to as hyperglycaemia and low levels are referred to as hypoglycaemia. One particular condition associated with a dysfunctional glucose homeostasis is hyperinsulinism. Hyperinsulinism (HI) is defined as the elevated insulin levels in blood due to dysregulated release of the insulin from β-cells and causes hypoglycaemia. It can be genetic or acquired and transient or permanent. Hyperinsulinaemic hypoglycaemia (HH) is described as a clinically, genetically, and morphologically heterozygous conditions where the insulin secretion is persistent despite low blood glucose levels. The most severe and permanent forms of HH is due to congenital hyperinsulinism. Congenital hyperinsulinism (CHI) is an inherited form of hyperinsulinaemic hypoglycaemia (HH) due to mutations in genes involved in the regulation of insulin secretion. CHI is a permanent form of hypoglycaemia in neonates, infants and children which causes irreversible brain damage due to the secondary metabolic actions of insulin. The excessive release of insulin causes suppression of lipolysis and reduction in ketones which are alternative energy sources for the brain. The rise of the insulin levels also inhibits secretion of glucagon Attorney Docket No.: R2054-7034WO which hinders the fat breakdown causing again direct damage of the brain. Therefore, up to 48% of children having recurrent hypoglycaemia suffer from brain damage. The genetic basis of CHI has been related to 23 mutations in essential genes controlling insulin secretion and two of these genes, namely ABCC8 and KCNJ11, are genes encoding KATP channel proteins SUR1 and Kir6.2, regulating the insulin release from the pancreatic β-cell among other proteins. In some embodiments, the metabolic disorder is obesity, e.g., hypothalamic obesity. In some embodiments, the metabolic disorder is diabetes, e.g., Type 1 or Type 2 diabetes, or first- phase diabetes or a pre-diabetes syndrome. In some embodiments, the metabolic disorder is a genetic or epigenetic disorder, e.g., Prader-Willi syndrome, Alström syndrome, Bardet-Biedl syndrome, or Smith-Magenis syndrome. In some embodiments, the metabolic disorder is Prader- Willi syndrome. In some embodiments, the metabolic disorder is Alström syndrome. In some embodiments, the metabolic disorder is Bardet-Biedl syndrome. In some embodiments, the metabolic disorder is Smith-Magenis syndrome. In an embodiment, the disease or disorder is ischemia. In some embodiments, the disease or disorder is alopecia or baldness. In an embodiment, the disease or disorder is a behavioral disorder or a psychological disorder. In some embodiments, the methods described herein directly or indirectly reduce or alleviate at least one symptom of a disease or disorder (e.g., a disease or disorder described herein). In some embodiments, the methods described herein may treat or alleviate at least one symptom of the metabolic disorder, e.g., an increase in waist circumference of at least 2 cm relative to a reference (e.g., the waist circumference of a subject before onset of the metabolic disorder); an increase in blood pressure relative to a reference (e.g., the blood pressure of a subject before onset of the metabolic disorder); hyperglycemia or an increase in fasting blood sugar relative to a reference (e.g., the fasting blood sugar of a subject before the onset of the metabolic disorder); an increase in thirst (e.g., an increase in thirst relative to a reference, e.g., the level of thirst of a subject before the onset the metabolic disorder); an increase in fatigue (e.g., an increase in fatigue relative to a reference, e.g., the level of fatigue of a subject before the onset of a metabolic disorder); or an increase in urination (e.g., an increase in urination relative Attorney Docket No.: R2054-7034WO to a reference, e.g., the frequency or amount of urination of a subject before the onset of a metabolic disorder). In some embodiments, the methods described herein prevents or slows the onset of a disease or disorder, e.g., a metabolic disorder. In some embodiments, the subject has a comorbidity, e.g., obesity, hyperphagia or hyperphagia-related syndromes, unwanted appetite, hypoglycemia, hyperglycemia, hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia. In some embodiments, the metabolic disorder is hyperinsulinemia, e.g., chronic hyperinsulinemia (CHI). In some embodiments, the metabolic disorder is pre-diabetes, type I diabetes, or type II diabetes. In some embodiments, the metabolic disorder is a diabetological condition. In some embodiments, the subject has had interventional surgery, e.g., bariatric surgery. In some embodiments, the subject has had brain surgery, e.g., a hypothalamic surgery. In some embodiments, the subject has a brain tumor, e.g., a craniopharyngioma, germinoma, glioma, hamartoma, pituitary adenoma. In some embodiments, the methods described herein may treat a metabolic disorder. In some embodiments, the methods described herein may provide a counterregulatory response to hypoglycemia in subject with diabetes, e.g., type I or type II diabetes. In some embodiments, the methods described herein may be useful in combination with a second agent, e.g., a sulfonylurea prior to a bolus to restore normal insulin levels in a subject, e.g., a subject with diabetes, e.g., type I or type II diabetes. In some embodiments, the disease or disorder is a cancer. In some embodiments, the cancer is a gastrointestinal cancer, e.g., oesophageal cancer, gastric cancer, pancreatic cancer, liver cancer, gallbladder cancer, colorectal cancer, anal cancer, or a gastrointestinal carcinoid tumour. In some embodiments, the gastrointestinal cancer is oesophageal cancer. In some embodiments, the gastrointestinal cancer is gastric cancer. In some embodiments, the gastrointestinal cancer is pancreatic cancer. In some embodiments, the gastrointestinal cancer is a pancreatic cancer, wherein the pancreatic cancer is an insulinoma. In some embodiments, the gastrointestinal cancer is liver cancer. In some embodiments, the gastrointestinal cancer is gallbladder cancer. In some embodiments, the gastrointestinal cancer is colorectal cancer. In some embodiments, the gastrointestinal cancer is anal cancer. In some embodiments, the gastrointestinal cancer is a gastrointestinal cancer. Attorney Docket No.: R2054-7034WO In some embodiments, the disease or disorder is a neurological disorder, e.g., Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis, migraine (e.g., chronic migraine), epilepsy and epilepsy-related syndromes. In some embodiments, the methods as described herein directly or indirectly reduce or alleviate at least one symptom of a disease or disorder, e.g., a neurological disease or disorder described herein. In some embodiments, the methods directly or indirectly reduce or alleviate pain or aid in pain management, i.e., the methods as described herein directly or indirectly function in analgesia of a disease or a disorder, e.g., a neurological disorder. In some embodiments, the methods as described herein directly or indirectly alleviate a symptom of a disease or disorder, e.g., a neurological disorder. In some embodiments, the methods as described herein provide neuroprotection in a subject in need thereof, e.g., in a subject with a neurological disorder, e.g., Alzheimer’s Disease, Parkinson’s Disease, or Multiple Sclerosis. In some embodiments, the disease or disorder is a cardiovascular disorder, e.g., ischemia, ischemia-reperfusion injury, hypertension, coronary spasm, ocular pressure, peripheral vascular disease. In some embodiments, the cardiovascular disorder is angina, cardioplegia, a ventricular septal defect, atrial fibrillation, arrythmia, coronary artery disease, or myocardial stunning. In some embodiments. the methods as described herein provide cardiooprotection in a subject in need thereof, e.g., in a subject with a cardiovascular disorder, e.g., angina, cardioplegia, a ventricular septal defect, atrial fibrillation, arrythmia, coronary artery disease, or myocardial stunning. In some embodiments, the disease or disorder is a pulmonary disorder, e.g., pulmonary hypertension or asthma. In some embodiments, the disease or disorder is an integumentary disorder, e.g., a disorder of the hair, skin, and nails, inter alia. In some embodiments, the disease or disorder is alopecia, baldness, e.g., male-pattern baldness, or disorders of hair follicular growth. In some embodiments, the disease or disorder is a sexual disorder, e.g., male impotence. In some embodiments, the disease or disorder is a urinary disorder, e.g., detrusor hyperreactivity. In an embodiment, the subject is a mammal, e.g., a human. In an embodiment, the subject is an adult (e.g., over the age of 18 years old) or a child (e.g., under the age of 18, 12, 10, 8, 6, 4, Attorney Docket No.: R2054-7034WO or 2 years old). In an embodiment, the subject has been treated for a metabolic disorder previously. For example, the subject may be a bariatric surgery patient. Combination Therapies Described herein are combination therapies comprising a potassium channel activator compound (i.e., a SURx / Kirx channel activator compound) and an MC4R agonist, useful for treating and / or a preventing a disease, disorder, or condition, such as obesity or an obesity- related disorder. The combination therapy may be administered as a single formulation or as separate formulations. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered as a single pharmaceutical composition. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered as separate pharmaceutical compositions. In the case of separate formulations, the SURx / Kirx channel activator compound and the MC4R agonist may be administered concomitantly or sequentially. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered concomitantly. In an embodiment, the SURx / Kirx channel activator compound and the MC4R agonist are administered sequentially. For example, the SURx / Kirx channel activator compound may be administered prior to the MC4R agonist or subsequent to the MC4R agonist. In some embodiments, the administration of the SURx / Kirx channel activator compound and the MC4R agonist has a synergistic or additive effect. For example, the SURx / Kirx channel activator compound and the MC4R agonist may have an additive effect, in which the therapeutic effect of the SURx / Kirx channel activator compound and the MC4R agonist is the total sum of the effects of each of the components individually. In contrast, the administration of the SURx / Kirx channel activator compound and the MC4R agonist may have a synergistic effect, in which the therapeutic effect of the SURx / Kirx channel activator compound and the MC4R agonist is greater than the sum of the individual components. The synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist may be 0.1%, 0.25%.0.5%.0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%.90%.95%, or more than the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist is greater than between 5% and 75% of the total sum of the Attorney Docket No.: R2054-7034WO effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist is greater than 10% of the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist is greater than 25% of the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination the SURx / Kirx channel activator compound and the MC4R agonist is greater than 50% of the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist is greater than 75% of the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. The synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist may be 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9- fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 40-fold, 50-fold, 75-fold, 100-fold, 200-fold, 500-fold greater or more than the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist is greater than between 2-fold and 100-fold of the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In an embodiment, the synergistic effect of the combination of the SURx / Kirx channel activator compound and the MC4R agonist is greater than between 5-fold and 50-fold of the total sum of the effects of the SURx / Kirx channel activator compound and the MC4R agonist administered individually. In one aspect, the amount of the SURx / Kirx channel activator compound and the MC4R agonist are selected such that the molar concentration of the SURx / Kirx channel activator compound is greater than the molar concentration of the MC4R agonist. For example, the molar concentration of the SURx / Kirx channel activator compound is greater than 1.5-fold, 2-fold, 3- fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 40- Attorney Docket No.: R2054-7034WO fold, 50-fold, 75-fold, 100-fold, 200-fold, or 500-fold greater than the molar concentration of the MC4R agonist. In an embodiment, the molar concentration of the SURx / Kirx channel activator compound is greater than 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, or 10-fold greater than the molar concentration of the MC4R agonist. In an embodiment, the molar concentration of the SURx / Kirx channel activator compound is between 2-fold and 20-fold greater than the molar concentration of the MC4R agonist. In an embodiment, the molar concentration of the SURx / Kirx channel activator compound is between 5-fold and 10-fold greater than the molar concentration of the MC4R agonist. In an embodiment, the molar concentration of the SURx / Kirx channel activator compound is about 5-fold greater than the molar concentration of the MC4R agonist. In an embodiment, the molar concentration of the SURx / Kirx channel activator compound is about 10-fold greater than the molar concentration of the MC4R agonist. In an embodiment, the molar concentration of the SURx / Kirx channel activator compound is about 15-fold greater than the molar concentration of the MC4R agonist. In another aspect, the combination of the SURx / Kirx channel activator compound and the MC4R agonist results in reducing the toxicity one or more of the SURx / Kirx channel activator compound and the MC4R agonist in a subject or cell when administered individually. For example, administration of a combination of the SURx / Kirx channel activator compound and the MC4R agonist may result in reducing the toxicity of the SURx / Kirx channel activator compound in a subject or cell, compared with the toxicity of the SURx / Kirx channel activator compound when administered to the subject or cell individually. In an embodiment, the toxicity of the SURx / Kirx channel activator compound in a subject or cell is reduced upon administration of SURx / Kirx channel activator compound in combination with an MC4R agonist, e.g., by about 0.1%, 0.25%.0.5%.0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%.90%.95%, or more compared with the toxicity of the SURx / Kirx channel activator compound when administered individually. In another aspect, the combination of the SURx / Kirx channel activator compound and the MC4R agonist results in reducing the toxicity of the MC4R agonist in a subject or cell. For example, administration of a combination of the SURx / Kirx channel activator compound may result in reducing the toxicity of the MC4R agonist in a subject or cell, compared with the toxicity of the MC4R agonist when administered to the subject or cell individually. In an embodiment, the toxicity of the SURx / Kirx channel activator compound in a subject or cell is Attorney Docket No.: R2054-7034WO reduced upon administration of an MC4R agonist in combination with a SURx / Kirx channel activator compound, e.g., by about 0.1%, 0.25%.0.5%.0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%.90%.95%, or more compared with the toxicity of the SURx / Kirx channel activator compound when administered individually. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 0.1 µM and 500 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 0.5 µM and 100 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 1 µM and 100 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 1 µM and 50 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 1 µM and 25 µM in a subject or cell. In an embodiment, the MC4R agonist is administered at a dosage to provide a concentration of between 0.01 µM and 50 µM in a subject or cell. In an embodiment, the MC4R agonist is administered at a dosage to provide a concentration of between 0.1 µM and 25 µM in a subject or cell. In an embodiment, the MC4R agonist is administered at a dosage to provide a concentration of between 0.1 µM and 10 µM in a subject or cell. In an embodiment, the MC4R agonist is administered at a dosage to provide a concentration of between 0.1 µM and 5 µM in a subject or cell. In an embodiment, the MC4R agonist is administered at a dosage to provide a concentration of between 0.1 µM and 2.5 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 0.1 µM and 500 µM and the MC4R agonist is administered at a dosage to provide a concentration of between 0.01 µM and 50 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 1 µM and 100 µM and the MC4R agonist is administered at a dosage to provide a concentration of between 0.1 µM and 25 µM in a subject or cell. In an embodiment, the SURx / Kirx channel activator compound is administered at a dosage to provide a concentration of between 1 µM and 25 µM and the MC4R agonist is administered at a dosage to provide a concentration of between 0.1 µM and 2.5 µM in a subject or cell. Attorney Docket No.: R2054-7034WO In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a therapeutic effect, e.g., allows for a subefficacious dosage of the SURx / Kirx channel activator compound, relative to the treatment of a disease or disorder or a symptom of a disease or disorder, for example, a (i) reduction in body weight, (ii) reduction in food intake, (iii) reduction in plasma blood glucose, (iv) reduction in plasma insulin, (v) reduction in plasma insulin, (vi) reduction in plasma leptin, (vii) reduction in a liver marker, such as steatosis, hepatocellular ballooning, lobular inflammation, lipid deposition, or total NAS. In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a reduction in body weight. In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a reduction in food intake. In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a reduction in plasma blood glucose. In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a reduction in plasma insulin. In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a reduction in plasma leptin. In an embodiment, the combination of the SURx / Kirx channel activator compound and the MC4R agonist administered to the subject allows for a reduction in the dosage of the SURx / Kirx channel activator compound needed to achieve a reduction in a liver marker, such as steatosis, hepatocellular ballooning, lobular inflammation, lipid deposition, or total NAS. In another aspect, the combination of the SURx / Kirx channel activator compound with an MC4R agonist results in reducing a symptom of a disease, disorder or condition in a subject. Attorney Docket No.: R2054-7034WO In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and has substantially no reduction in body weight, e.g., relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 1% and 40%, e.g., 5% and 30%, e.g., relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 18-20%, e.g., relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.1. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 20-25% after 22 days, e.g., relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.12A. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 18-20% after 22 days relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.13. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 15-20% after 22 days relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.12B. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 18-20% after 22 days relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.16A. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in body weight of between 18-20% after 22 days relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.16B. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides a reduction in plasma glucose relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in plasma glucose between about 1% and 50% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to subject and provides a reduction in plasma glucose of between 30-40% Attorney Docket No.: R2054-7034WO relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.3A. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma glucose between about 25% -45% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.7A. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides a reduction in plasma insulin relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in plasma insulin between about 1% and 90% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to subject and provides a reduction in plasma insulin of between 70-90% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.3B. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to subject and provides a reduction in plasma insulin of between 65-75% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.7B. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides a reduction in plasma leptin relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in plasma leptin between about 1% and 50% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to subject and provides a reduction in plasma leptin of between 30-50% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.3C. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides a reduction in plasma glucose relative to a reference standard, e.g., a placebo,. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in plasma glucose of about 100-400mg / dL relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction in plasma glucose of about 300-400 mg / dL relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.4A. In some embodiments, the Attorney Docket No.: R2054-7034WO SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction in plasma glucose of about 100-200 mg / dL relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.8A. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction in plasma glucose of about 100-200 mg / dL relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.8B. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides a reduction in plasma insulin relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject an provides a reduction in plasma insulin of about 1-10 ng / mL relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction in plasma insulin of about 4-8 ng / dL relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.4B. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction in plasma insulin of about 5-10 ng / dL relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.8C. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction in plasma insulin of about 5-10 ng / dL relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.8D. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides no substantial reduction in body weight relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist to a subject and provides a reduction in body weight of about 1-30% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction of 10-20% relative to a reference standard, e.g., a placebo, as shown in FIG.5. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides no substantial reduction in body weight relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered with an MC4R agonist to a subject and provides a reduction in body weight of about 1-40 g relative to a reference standard, e.g., a placebo. In some embodiments, the Attorney Docket No.: R2054-7034WO SURx / Kirx channel activator compound is administered with an MC4R agonist and provides a reduction of 20-40 g relative to a reference standard, e.g., a placebo, as shown in FIG.6. In some embodiments, the SURx / Kirx channel activator compound is administered to a subject as a single therapy and provides no substantial reduction in cumulative food intake relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in cumulative food intake of about 10-500 g after 22 days relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction of 200-400 g after 22 days relative to a reference standard, e.g., a placebo, as shown in FIG.2. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction of 200-400 g after 22 days relative to a reference standard, e.g., a placebo, as shown in FIG.2B. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction of 200-400 g after 22 days relative to a reference standard, e.g., a placebo, as shown in FIG.17A. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction of 200-400 g after 22 days relative to a reference standard, e.g., a placebo, as shown in FIG.17B. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in glucose area-under-the-curve (AUC) relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in glucose area-under-the-curve (AUC) of about 10-200 mg / (dL·h) after 120 min relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in glucose area-under-the-curve (AUC) of 100-200 mg / (dL·h) after 120 min relative to a reference standard, e.g., a placebo, as shown in FIG.9A. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in glucose area-under-the-curve (AUC) of 100-200 mg / (dL·h) after 120 min relative to a reference standard, e.g., a placebo, as shown in FIG.9B. Attorney Docket No.: R2054-7034WO In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in insulin area-under-the-curve (AUC) relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in insulin area-under-the-curve (AUC) of about 1-15 ng / (mL·h) after 120 min relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in glucose area-under-the-curve (AUC) of 5-10 ng / (mL·h) after 120 min relative to a reference standard, e.g., a placebo, as shown in FIG.9C. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides a reduction in glucose area-under-the-curve (AUC) of 5-10 ng / (mL·h) after 120 min relative to a reference standard, e.g., a placebo, as shown in FIG.9D. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial change in plasma cholesterol relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides no substantial change in plasma cholesterol relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist to a subject and provides no substantial change in plasma cholesterol relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.10A. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in plasma triglycerides relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma triglycerides of about 1-10 mmol / L relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma triglycerides of about 5-10 mmol / L relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.10A. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in plasma NEFA relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is Attorney Docket No.: R2054-7034WO administered in combination with an MC4R agonist and provides a reduction in plasma NEFA of about 100-1000 µM relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma NEFA of about 400-800 µM relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.10B or in FIG.10D. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in plasma AST relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma AST of about 1-20 U / L relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma AST of about 10-20 U / L relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.10C. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial reduction in plasma ALT relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma ALT of about 1-20 U / L relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in plasma ALT of about 10-20 U / L relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.10D. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial reduction in liver cholesterol relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist a provides a reduction in liver cholesterol of about 0.1-0.5 mg / g relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist a provides a reduction in liver cholesterol of about 0.1-0.3 mg / g relative to a reference standard, e.g., a placebo, e.g. as shown in FIG.11. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial reduction in liver NEFA relative to a reference Attorney Docket No.: R2054-7034WO standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist a provides a reduction in liver NEFA of about 0.1-0.5 mg / g relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist a provides a reduction in liver NEFA of about 0.1-0.3 mg / g relative to a reference standard, e.g., a placebo, e.g. as shown in FIG.11. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial reduction in liver triglycerides relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in liver triglycerides of about 10-100 mg / g relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in liver triglycerides of about 30-60 mg / g relative to a reference standard, e.g., a placebo, e.g. as shown in FIG.11. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial reduction in liver glycogen relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides no substantial reduction in liver glycogen relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides no substantial reduction in liver glycogen relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.11. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in steatosis score relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in steatosis score of about 0.1 to 2 relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in steatosis score of about 1 to 2 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.14. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in Attorney Docket No.: R2054-7034WO steatosis score of about 1 to 2 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.15. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in vacuolation score relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in vacuolation score of about 0.1 to 2 relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in vacuolation score of about 1 to 2 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.14. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in vacuolation score of about 1 to 2 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.15. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in inflammatory infiltration score relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in inflammatory infiltration score of about 0.1 to 3 relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in vacuolation score of about 2 to 3 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.14. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in vacuolation score of about 1 to 2 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.15. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in lipid deposition score relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in lipid deposition score of about 0.1 to 4 relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in lipid deposition score of about 2 to 4 relative to a reference standard, Attorney Docket No.: R2054-7034WO e.g., a placebo, e.g., as shown in FIG.14. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in lipid deposition score of about 2 to 4 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.15. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has a reduction in total NAS score relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in total NAS score of about 0.1 to 8 relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in lipid deposition score of about 4 to 8 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.14. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in lipid deposition score of about 4 to 8 relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.15. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial change in carcass weight relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in carcass weight of between about 1-25% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in carcass weight of 15-20% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.19A. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has no substantial change in fat relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in fat of between about 10-40% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in fat of 20-30% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.19B. Attorney Docket No.: R2054-7034WO In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has an increase in protein of about 10-30% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in protein of between about 0-10% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides no change in protein relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in protein of 5% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.19C. In some embodiments, the SURx / Kirx channel activator compound administered in combination with an MC4R agonist reduces fat tissue in a subject has a lower (e.g., substantially lower) reduction in lean muscle mass, e.g., protein. In some embodiments, the SURx / Kirx channel activator compound is administered as a single therapy and the subject has an increase in water of about 1-20% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in water of between about 5-15% relative to a reference standard, e.g., a placebo. In some embodiments, the SURx / Kirx channel activator compound is administered in combination with an MC4R agonist and provides a reduction in water of 10% relative to a reference standard, e.g., a placebo, e.g., as shown in FIG.19D. In some embodiments, the SURx / Kirx channel activator concentration in the CSF is between about 100-1000 ng / mL when administered as a monotherapy. In some embodiments, the SURx / Kirx channel activator concentration in the liver is between about 10,000-100,000 ng / mL when administered as a monotherapy. In some embodiments, the SURx / Kirx channel activator plasma concentration is between about 10,000-100,000 ng / mL when administered as a monotherapy. In some embodiments, the SURx / Kirx channel activator concentration in the CSF is between about 606 ng / mL when administered as a monotherapy, e.g., as shown in FIG.18. In some embodiments, the SURx / Kirx channel activator concentration in the liver is between about 25,133 ng / mL when administered as a monotherapy, e.g., as shown in FIG.18. In some embodiments, the SURx / Kirx channel activator plasma concentration is between about 27,600 ng / mL, when administered as a monotherapy, e.g., as shown in FIG.18. Attorney Docket No.: R2054-7034WO In some embodiments, the SURx / Kirx channel activator concentration in the CSF is between about 100-1000 ng / mL when administered as a combination therapy with an MC4R agonist. In some embodiments, the SURx / Kirx channel activator concentration in the liver is between about 10,000-100,000 ng / mL when administered as a combination therapy with an MC4R agonist. In some embodiments, the SURx / Kirx channel activator plasma concentration is between about 10,000-100,000 ng / mL when administered as a combination therapy with an MC4R agonist. In some embodiments, the SURx / Kirx channel activator concentration in the CSF is between about 429 ng / mL when administered as a combination therapy with an MC4R agonist, e.g., as shown in FIG.18. In some embodiments, the SURx / Kirx channel activator concentration in the liver is between about 23,714 ng / mL when administered as a combination therapy with an MC4R agonist, e.g., as shown in FIG.18. In some embodiments, the SURx / Kirx channel activator plasma concentration is between about 31,371 ng / mL when administered as a combination therapy with an MC4R agonist, e.g., as shown in FIG.18. In some embodiments, the MC4R concentration in the CSF is between about 0.01-1 ng / mL when administered as a combination therapy with an SURx / Kirx channel activator compound. In some embodiments, the SURx / Kirx channel activator concentration in the liver is between about 1-100 ng / mL when administered as a combination therapy with an SURx / Kirx channel activator compound. In some embodiments, the SURx / Kirx channel activator plasma concentration is between about 1-100 ng / mL when administered as a combination therapy with an MC4R agonist. In some embodiments, the MC4R concentration in the CSF is between about 0.59 ng / mL when administered as a combination therapy with an SURx / Kirx channel activator compound, e.g., as shown in FIG.18. In some embodiments, the SURx / Kirx channel activator concentration in the liver is between about 12.7 ng / mL when administered as a combination therapy with an SURx / Kirx channel activator compound, e.g., as shown in FIG.18. In some embodiments, the SURx / Kirx channel activator plasma concentration is between about 27.6 ng / mL when administered as a combination therapy with an MC4R agonist, e.g., as shown in FIG.18. Routes of Administration and Dosages The compounds and compositions, according to the method of the present invention, are administered using any amount and any route of administration effective for treating or lessening Attorney Docket No.: R2054-7034WO the severity of a disorder provided above. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the infection, the particular agent, its mode of administration, and the like. Compounds of the invention are preferably formulated in dosage unit form for ease of administration and uniformity of dosage. The expression "dosage unit form" as used herein refers to a physically discrete unit of agent appropriate for the patient to be treated. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific effective dose level for any particular patient or organism will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed, and like factors well known in the medical arts. Pharmaceutically acceptable compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, as an oral or nasal spray, or the like, depending on the severity of the infection being treated. In certain embodiments, the compounds of the invention are administered orally or parenterally at dosage levels of about 0.01 mg / kg to about 100 mg / kg and preferably from about 1 mg / kg to about 50 mg / kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect. Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms optionally contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures Attorney Docket No.: R2054-7034WO thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions are formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation are also a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer’s solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. In some embodiments, a triglyceride or a plurality of triglycerides (e.g., medium chain triglycerides or long chain triglycerides) are used in the preparation of the injectable. In other embodiments, a phospholipid or a plurality of phospholipids are used in the preparation of the injectable. Injectable formulations can be sterilized, for example, by filtration through a bacterial- retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. In order to prolong the effect of a compound of the present invention, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This is accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compound then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compound form is accomplished by dissolving or suspending the compound in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compound in biodegradable polymers such as polylactide- polyglycolide. Depending upon the ratio of compound to polymer and the nature of the particular polymer employed, the rate of compound release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the compound in liposomes or microemulsions that are compatible with body tissues. Attorney Docket No.: R2054-7034WO Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and / or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar--agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, acetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form also optionally comprises buffering agents. Solid compositions of a similar type are also employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type are also employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like. The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and Attorney Docket No.: R2054-7034WO granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms optionally also comprise buffering agents. They optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as required. Ophthalmic formulation, ear drops, and eye drops are also contemplated as being within the scope of this invention. Additionally, the present invention contemplates the use of transdermal patches, which have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. ENUMERATED EMBODIMENTS 1. A method of treating a disease or disorder in a subject, the method comprising administering a combination of: (i) a potassium channel activator (e.g., SURx / Kirx channel activator compound) or a pharmaceutically acceptable salt thereof; and (ii) an MC4R agonist, to the subject, thereby treating the disease or disorder in the subject. Attorney Docket No.: R2054-7034WO 2. The method of embodiment 1, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XIV): R5Rxor a pharmaceutically A is C(R’); each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; X is C(R’) or S; when X is C (R’) then Y is C(R’); or, when X is S, then Y is absent; each of R1, R2, R5, and R6 are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rxis hydrogen or wherein A and D form a double bond and Ry is hydrogen; R3 is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4; R’ is absent, hydrogen, or C1-C6 alkyl; each R4is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, Attorney Docket No.: R2054-7034WO alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano. 3. The method of any one of the preceding embodiments, wherein the SURx / Kirx channel activator compound is diazoxide or a pharmaceutically acceptable salt thereof. 4. The method of any one of the preceding embodiments, wherein the SURx / Kirx channel activator compound is 3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1- dioxide or a pharmaceutically acceptable salt thereof. 5. The method of any one of the preceding embodiments, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XIII): R5Rxor a pharmaceutically A is C(R’); each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; each of R1, R2, R5, and R6are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rx is hydrogen or wherein A and D form a double bond and Ryis hydrogen; Attorney Docket No.: R2054-7034WO R3 is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4; R’ is absent, hydrogen, or C1-C6 alkyl; each R4 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano. 6. The method of any one of the preceding embodiments, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XIV): R5Rxor a pharmaceutically or isotope thereof, wherein: A is C(R’); Attorney Docket No.: R2054-7034WO each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; X is C(R’) or S; when X is C (R’) then Y is C(R’); or, when X is S, then Y is absent; each of R1, R2, R5, and R6are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rx is hydrogen or wherein A and D form a double bond and Ryis hydrogen; R3is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4; R’ is absent, hydrogen, or C1-C6 alkyl; each R4 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano. 7. The method of any one of the preceding embodiments, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XV): Attorney Docket No.: R2054-7034WO OOS R2R N , wherein: R represents hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, alkoxyalkyl, alkylthio, alkylcarbonyl, phenylcarbonyl, phenylsulfonyl, phenylsulfinyl, phenyloxy, phenylthio, where the phenyl radicals can be substituted by alkyl, alkoxy, halogen, nitro or amino, or for thenoyl or pyridylcarbonyl, which can be substituted by alkyl; R1is hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, alkoxyalkyl, alkylthio, alkylcarbonyl, phenylcarbonyl, phenylsulfonyl, phenylsulfinyl, phenyloxy or phenylthio, the phenyl radicals being represented by alkyl, alkoxy , halogen, nitro or amino can be substituted, or stands for thenoyl or pyridylcarbonyl, whereby these can be substituted by alkyl; R2stands for hydrogen or alkyl; R3stands for hydrogen or alkyl; R4stands for the NH2, NHR5or the NR5R6- Group, where the radicals R5and R6can be identical or different and are alkyl or phenyl or phenylalkyl, and in the case of v on R5- alkyl this group can be connected to a carbon atom of the alkylene group to form a 5- or 6- membered ring, or where the radicals R5and R6together with the nitrogen atom can form an optionally substituted azabicycloalkyl radical with 6 to 10 ring members or R represents a cycloalkyleneimino group optionally interrupted by O, S, NH or NR5and / or substituted by one or two alkyl groups with a total of 5 to 7 ring members and in which the ring can optionally contain one, two or three double bonds, and alkylene represents a divalent alkylene group, which can optionally be substituted by alkyl and / or by a hydroxy, acyloxy or alkoxy group, and their physiologically compatible salts. 8. The method of any one of the preceding embodiments, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XVI): Attorney Docket No.: R2054-7034WO Y H H R1N N X R2, wherein X and Y independently are C1-6-alkyl or C1-6-alkoxy; R1, R2and R3independently are C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, carboxy, C1-6-alkoxycarbonyl or aryl, all of which are optionally being mono- or polysubstituted with halogen, hydroxy, oxo, or aryl; or R1is as defined above and R2-C-R3form a C3-6 -cyeloalkyl group, optionally being mono- or polysubstituted with C1-6-alkyl, perhalomethyl, halogen, hydroxy or aryl; or -CR1R2R3form a 4- to 12-membered bicyclic or tricyclic carbocyciic system, optionally being mono- or polysubstituted with C.-6-alkyl, perhalomethyl, halogen, hydroxy or aryl; or a salt thereof with a pharmaceutically acceptable acid or base including all optical isomers of compounds of formula I, some of which are optically active, and also their mixtures including racemic mixtures, or any tautomeric form thereof. 9. The method of any of the preceding embodiments, SURx / Kirx channel activator compound is selected from: 3-tert-butylamino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-(1,1-dimethylpropylamino)-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-(2-hydroxy-1,1-dimethylethylamino)-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1- dioxide; 6-Chloro-3-(1,1,3,3-tetramethylbutylamino)-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1- dioxide; 3-(1-adamantyl)amino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1 -dioxide; 1-(6-Chloro-1 ,4-dihydro-1,1-dioxo-thieno[3,2-e]-1λ6,2,4-thiadiazin-3-ylamino)- cyclopropanecarboxylic acid ethyl ester; 6-Chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1- dioxide; Attorney Docket No.: R2054-7034WO 6-Chloro-3-(1-hydroxymethylcyclopentyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1- dioxide; 1-(6-Chloro-1,4-dihydro-1,1-dioxo-thieno[3,2-e]-1λ6,2,4-thiadiazin-3-ylamino)- cyclopropanecarboxylic acid; 6-Chloro-3-(1-methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-(1-methylcyclohexyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1 -dioxide; 6-Chloro-3-(1-methylcyclopentyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; and 6-Chloro-3-(1-ethylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide. 10. The method of any of the preceding embodiments, SURx / Kirx channel activator compound is selected from a compound in the Table below: Compound Structure Name No. SURx / Kirx H N 7-chloro-3-methyl-4H-1,2,4- channel benzothiadiazine 1,1-dioxide activator N compound I Cl S OOSURx / Kirx H H N 6-chloro-3-[[11- channel N methylcycloproyl]amino]-4H- activator Cl S N thieno[3,2-e]-1,2,4-thiadiazine 1,1- compound II S OOdioxide 1HH N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-fluoro-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide 2HH 7-fluoro-3-((1- N N methylcyclobutyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide 3HH N N 7-fluoro-3-((3- fluorobicyclo[1.1.1]pentan-1- N F yl)amino)-4H- F S OObenzo[e][1,2,4]thiadiazine 1,1- dioxide Attorney Docket No.: R2054-7034WO H H 3-(bicyclo[2.1.1]hexan-1-ylamino)- N N 7-fluoro-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N 3-((2,2-dimethylcyclopropyl)amino)- 7-fluoro-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N (S*)-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide H H N N (R*)-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide H H N 7-fluoro-3-(spiro[2.2]pentan-1- N ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N (S*)-7-fluoro-3-(spiro[2.2]pentan-1- N ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N (R*)-7-fluoro-3-(spiro[2.2]pentan-1- ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H N N 7-fluoro-3-(spiro[2.3]hexan-1- ylamino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 3-((1-ethylcyclopropyl)amino)-7- N fluoro-4H-benzo[e][1,2,4]thiadiazine F S 1,1-dioxide OOHH 3-([1,1’-bi(cyclopropan)]-1- N N ylamino)-7-fluoro-4H- benzo[e][1,2,4]thiadiazine 1,1- N F S dioxide OO Attorney Docket No.: R2054-7034WO ClHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-chloro-7-fluoro-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide) H H l 6-chloro-7-fluoro NN-3- (spiro[2.3]hexan-1-ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H l (S*)-6-chloro-7-fluoro NN-3- (spiro[2.3]hexan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H H l (R*)-6-chloro-7-fluoro-3- NN(spiro[2.3]hexan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H H l 6-chloro-7-fluoro-3-((3- NNmethylbicyclo[1.1.1]pentan-1- N yl)amino)-4H- F S OObenzo[e][1,2,4]thiadiazine 1,1- dioxidelHH N 6-chloro-7-fluoro-3-((3- N fluorobicyclo[1.1.1]pentan-1- N yl)amino)-4H- F S F OObenzo[e][1,2,4]thiadiazine 1,1- dioxide lHN H N 6-chloro-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide lHN H N (S*)-6-chloro-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxide lHN H N (R*)-6-chloro-3-((2,2- dimethylcyclopropyl)amino)-7- N F S fluoro-4H-benzo[e][1,2,4]thiadiazine OO1,1-dioxideClHH NN CF36-chloro-7-fluoro-3-((1- (trifluoromethyl)cyclopropyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide Attorney Docket No.: R2054-7034WO ClHH 6-chloro-7-fluoro NN-3-((1- methylcyclobutyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxideClHH NN(rac)-trans-6-chloro-7-fluoro-3-((2- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxideClHH NN6-chloro-7-fluoro-3-(((1S*,2S*)-2- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]-thiadiazine 1,1- OOdioxideClHH NN6-chloro-7-fluoro-3-(((1R*,2R*)-2- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]-thiadiazine 1,1- OOdioxideClHH NN6-chloro-7-fluoro-3- (spiro[2.2]pentan-1-ylamino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H HCl(S*)-6-chloro-7-fl NNuoro-3- (spiro[2.2]pentan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H HClN(R*)-6-chloro-7-fluoro-3- N (spiro[2.2]pentan-1-ylamino)-4H- N benzo[e][1,2,4]-thiadiazine 1,1- F S OOdioxide H H ClN3-(bicyclo[2.1.1]hexan-1-ylamino)- N 6-chloro-7-fluoro-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide FHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6,7-difluoro-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxideFHH N 6,7-difluoro-3-(spiro[2.3]hexan-1- N ylamino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide Attorney Docket No.: R2054-7034WOFHH 6,7-difluoro- NN3-((1- methylcyclobutyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H FNN 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-chloro-6-fluoro-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-chloro-8-fluoro-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- FO Odioxide BrHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-bromo-4H-benzo[e]- N S [1,2,4]thiadiazine 1,1-dioxide OOH H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 8-bromo-4H- N S benzo[e][1,2,4]thiadiazine 1,1- BrO Odioxide IHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-iodo-4H-benzo[e][1,2,4]thiadiazine N S 1,1-dioxide OOH H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 6-methyl-4H- N S benzo[e][1,2,4]thiadiazine 1,1- OOdioxideNCHH NN3-(bicyclo[1.1.1]pentan-1-ylamino)- 4H-benzo[e][1,2,4]-thiadiazine-6- N S carbonitrile 1,1-dioxide OOH H N N 3-(tert-butylamino)-7-fluoro-4H- benzo[e][1,2,4]thiadiazine 1,1- N F S dioxide OOH H N N 3-((1,3-difluoropropan-2-yl)amino)- F 7-fluoro-4H- N SFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide Attorney Docket No.: R2054-7034WO H H N N 7-fluoro-3-((1-(dimethylamino)-2- N methylpropan-2-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N O 7-fluoro-3-((4-methoxy-2- methylbutan-2-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- F (fluoromethyl)cyclopropyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N O 7-chloro-3-((4-methoxy-2- methylbutan-2-yl)amino)-4H- N l S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1,3-difluoropropan-2- F yl)amino)-4H- ClN SFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1-(dimethylamino)-2- N methylpropan-2-yl)amino)-4H- N l S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- methylcyclopropyl)amino)-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- F (fluoromethyl)cyclopropyl)amino)- N Cl S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((3,3- difluorocyclobutyl)amino)-4H- N FClSFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 3-(tert-butylamino)-6-chloro-7- fluoro-4H-benzo[e][1,2,4]thiadiazine N F S 1,1-dioxide OO Attorney Docket No.: R2054-7034WO H H Cl N N 6-chloro-3-((1,3-difluoropropan-2- F yl)amino)-7-fluoro-4H- F N SFbenzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-3-((1-(dimethylamino)-2- N methylpropan-2-yl)amino)-7-fluoro- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H l N N O 6-chloro-7-fluoro-3-((4-methoxy-2- methylbutan-2-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- methylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-3-((1- ethynylcyclopropyl)amino)-7-fluoro- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- F (fluoromethyl)cyclopropyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-3-((3,3- F difluorocyclobutyl)amino)-7-fluoro- F N SF4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 3-(bicyclo[1.1.1]pentan-1-ylamino)- 7-chloro-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H 7-fluoro-3-((1- N N isopropylcyclopropyl)amino)-4H- N benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- isopropylcyclopropyl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide Attorney Docket No.: R2054-7034WO H H N N 7-fluoro-3-((1- O (methoxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-fluoro-3-((1- OH (hydroxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- O (methoxymethyl)cyclobutyl)amino)- N Cl S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N 7-chloro-3-((1- OH (hydroxymethyl)cyclobutyl)amino)- N Cl S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- O (methoxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N 6-chloro-7-fluoro-3-((1- OH (hydroxymethyl)cyclobutyl)amino)- N F S 4H-benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N (R)-7-fluoro-3-((tetrahydrofuran-3- O yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H N N (R)-7-chloro-3-((tetrahydrofuran-3- O yl)amino)-4H- N Cl S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H H Cl N N (R)-6-chloro-7-fluoro-3- O ((tetrahydrofuran-3-yl)amino)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide H NN(R)-7-fluoro-3-(2- (hydroxymethyl)azetidin-1-yl)-4H- N OH benzo[e][1,2,4]thiadiazine 1,1- F S OOdioxide Attorney Docket No.: R2054-7034WO 75 H NN(R)-7-chloro-3-(2- (hydroxymethyl)azetidin-1-yl)-4H- N OH benzo[e][1,2,4]thiadiazine 1,1- Cl S OOdioxide 76 H ClN N(R)-6-chloro-7-fluoro-3-(2- OH (hydroxymethyl)azetidin-1-yl)-4H- N F S benzo[e][1,2,4]thiadiazine 1,1- OOdioxide 11. The method of any one of the preceding embodiments, wherein the MC4R agonist is a peptide or a small molecule. 12. The method of any one of the preceding embodiments, wherein the MC4R agonist is a peptide. 13. The method of any one of the preceding embodiments, wherein the MC4R agonist has the structure of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII) or a pharmaceutically acceptable salt thereof, e.g., as described herein. 14. The method of any one of the preceding embodiments, wherein the MC4R agonist has the structure of Formula (I), or a pharmaceutically acceptable salt thereof, e.g., as described herein. 15. The method of embodiment 14, wherein R2is Ac. 16. The method of embodiment 14, wherein R3is H. 17. The method of embodiment 14, wherein R1is NH2. 18. The method of embodiment 14, wherein A1 is Arg. 19. The method of embodiment 14, wherein A2is Cys. Attorney Docket No.: R2054-7034WO 20. The method of embodiment 14, wherein A9is Cys. 21. The method of embodiment 14, wherein A3is deleted. 22. The method of embodiment 14, wherein A4is His. 23. The method of embodiment 14, wherein A5is D-(X1, X2, X3, X4, X5)Phe. 24. The method of embodiment 14, wherein A5is D-Phe. 25. The method of embodiment 14, wherein A6is Arg. 26. The method of embodiment 14, wherein A7is Trp. 27. The method of embodiment 14, wherein A8is deleted. 28. The method of any one of the preceding embodiments, wherein the MC4R agonist is selected from: (SEQ ID NO: 1) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 2) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; (SEQ ID NO: 3) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 4) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 5) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 6) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; (SEQ ID NO: 7) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 8) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; (SEQ ID NO: 9) Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 10) Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 11) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 12 ) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 13) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 14) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 15) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 16) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 17) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 18) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 19) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 20) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 21) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 22) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 23) Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 24) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 25) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 26) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 27) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 28) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 29) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 30) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 31) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 32) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 33) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 34) Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 35) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 36) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 37) Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 38) Ac-D-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 39) Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 40) Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 41) Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 42) Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 43) Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 44) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 45) n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 46) n-butyryl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 47) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 48) Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 49) Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 50) Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 51) Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 52) Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 53) Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 54) Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 55) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 56) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 57) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 58) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; (SEQ ID NO: 59) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; (SEQ ID NO: 60) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; (SEQ ID NO: 61) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 62) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 63) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; (SEQ ID NO: 64) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; (SEQ ID NO: 65) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 66) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 67) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 68) n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 69) n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 70) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 71) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 72) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; (SEQ ID NO: 73) Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 74) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 75) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; (SEQ ID NO: 76) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 77) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 78) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 79) D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 80) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 81) D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 82) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 83) D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 84) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 85) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 86) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; (SEQ ID NO: 87) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; (SEQ ID NO: 88) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; (SEQ ID NO: 89) Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 90) Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)- NH2; (SEQ ID NO: 91) Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 92) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 93) Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 94) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 95) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 96) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 97) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 98) Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 99) Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 100) Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 101) Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 102) Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 103) Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 104) Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 105) Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 106) Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 107) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; (SEQ ID NO: 108) Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)- NH2; (SEQ ID NO: 109) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; (SEQ ID NO: 110) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 111) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 112) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 113) Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 114) Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 115) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; (SEQ ID NO: 116) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; (SEQ ID NO: 117) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; (SEQ ID NO: 118) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; (SEQ ID NO: 119) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; (SEQ ID NO: 120) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; (SEQ ID NO: 121) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; (SEQ ID NO: 122) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 123) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 124) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 125) Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 126) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 127) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 128) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; (SEQ ID NO: 129) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; (SEQ ID NO: 130) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; (SEQ ID NO: 131) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; (SEQ ID NO: 132) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; (SEQ ID NO: 133) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; (SEQ ID NO: 134) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; (SEQ ID NO: 135) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; (SEQ ID NO: 136) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 137) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; (SEQ ID NO: 138) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; (SEQ ID NO: 139) Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 140) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 141) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 142) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 143) Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 144) Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 145) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 146) Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; and (SEQ ID NO: 147) Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2, or a pharmaceutically acceptable salt thereof. 29. The method of any one of the preceding embodiments, wherein the MC4R agonist is: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 140), or a pharmaceutically acceptable salt thereof. 30. The method of any of the preceding embodiments, wherein the MC4R agonist compound is a compound of Formula (I-a): H-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-NH2(I-a) or a pharmaceutically acceptable salt thereof, wherein: A1is Phe, D-Phe, or Nle; A2is Cys; A3is deleted; A4is His; A5is D-Phe or D-(Et)Tyr; A6is Arg or hArg; A7is Trp or Bip; A8is Ala, β-Ala, Gaba, or Apn; A9is D-Cys; and A10is Thr or deleted. Attorney Docket No.: R2054-7034WO 31. The method of any of the preceding embodiments, wherein the compound is a compound of Formula (I-a) is selected from: SEQ ID NO: 4) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 5) D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 6) D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; (SEQ ID NO: 79) D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 80) D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 81) D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 82) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 83) D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 84) D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; (SEQ ID NO: 85) Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; and (SEQ ID NO: 105) Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2. 32. The method of any of the preceding embodiments, wherein the MC4R agonist compound is a compound of Formula (I-b): Ac-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-NH2 (I-b) or a pharmaceutically acceptable salt thereof, wherein: A1is Nle, A6c, D-2-Nal, Cha, Oic, Chg, hCha, D-Cha, D-hCha, Nip, hPro, hLeu, Phe, D- Phe, D-Chg, hPhe, β-hMet, Gaba, Leu, Ile, Val, 2-Nal, Arg or D-Arg; A2is Asp, Cys, D-Cys, or Pen; A3is D-Ala, β-Ala, Gaba, Aib, Gly, Ala, D-Glu, D-Abu, D-Val, D-Ile, D-Leu, D-Tle, D- Cha, deleted; A4His or 3-Pal; A5is Phe, D-Phe, or D-2-Nal; A6is Arg; A7is Trp, 1-Nal, 2-Nal, Bal, or D-Trp; A8is β-Ala, A6c, Ahx, Apn, Gaba, Ala, Aha, D-Ala or deleted; A9is Lys, Cys, D-Cys, or Pen; A10is deleted. Attorney Docket No.: R2054-7034WO wherein A2and A9are pairwise selected to form a disulfide or lactam bridge. 33. The method of any one of the preceding embodiments, wherein the compound of Formula (I-b) is: (SEQ ID NO: 1) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 2) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; (SEQ ID NO: 3) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 7) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; (SEQ ID NO: 8) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; (SEQ ID NO: 9) Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 10) Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 11) Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 12 ) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 13) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 14) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 15) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 16) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 17) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 18) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 19) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 20) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 21) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 22) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 23) Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 24) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 25) Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 26) Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 27) Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 28) Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 29) Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 30) Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 31) Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 32) Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 33) Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; (SEQ ID NO: 34) Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 35) Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 36) Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 37) Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 38) Ac-D-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 39) Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 40) Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 41) Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 42) Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 43) Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 44) Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 47) Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 48) Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 49) Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 50) Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 51) Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 52) Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 53) Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 54) Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; (SEQ ID NO: 55) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 56) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 57) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 58) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; (SEQ ID NO: 59) Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; (SEQ ID NO: 60) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; (SEQ ID NO: 61) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 62) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 63) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 64) Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; (SEQ ID NO: 65) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 66) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 67) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 70) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; (SEQ ID NO: 71) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; (SEQ ID NO: 72) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; (SEQ ID NO: 73) Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 74) Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; (SEQ ID NO: 75) Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; (SEQ ID NO: 76) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 77) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 78) Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 86) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; (SEQ ID NO: 87) Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; (SEQ ID NO: 89) Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 90) Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)- NH2; (SEQ ID NO: 91) Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 92) Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 93) Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 94) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 95) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 96) Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 97) Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 98) Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 99) Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 100) Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 101) Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 102) Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 103) Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 106) Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; Attorney Docket No.: R2054-7034WO (SEQ ID NO: 108) Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)- NH2; (SEQ ID NO: 109) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; (SEQ ID NO: 110) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; (SEQ ID NO: 111) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; (SEQ ID NO: 112) Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; (SEQ ID NO: 113) Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 114) Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; (SEQ ID NO: 139) Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (SEQ ID NO: 140) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 141) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEQ ID NO: 142) Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 143) Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 144) Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; (SEQ ID NO: 145) Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 146) Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; and (SEQ ID NO: 147) Ac-Arg-c(Asp-His-D-Phe-Arg-Tr...

Claims

Attorney Docket No.: R2054-7034WO CLAIMS 1. A method of treating a disease or disorder in a subject, the method comprising administering a combination of: (iii) a potassium channel activator (e.g., SURx / Kirx channel activator compound) or a pharmaceutically acceptable salt thereof; and (iv) an MC4R agonist, to the subject, thereby treating the disease or disorder in the subject.

2. The method of claim 1, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XIV): R5Rxor a pharmaceuticallyA is C(R’); each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; X is C(R’) or S; when X is C (R’) then Y is C(R’); or, when X is S, then Y is absent; each of R1, R2, R5, and R6are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rx is hydrogen or wherein A and D form a double bond and Ry is hydrogen; R3is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4;Attorney Docket No.: R2054-7034WO R’ is absent, hydrogen, or C1-C6 alkyl; each R4 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano.

3. The method of claim 1, wherein the SURx / Kirx channel activator compound is diazoxide or a pharmaceutically acceptable salt thereof.

4. The method of claim 1, wherein the SURx / Kirx channel activator compound is 3-(1- methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide or a pharmaceutically acceptable salt thereof.

5. The method of claim 1, wherein the SURx / Kirx channel activator compound is a compound having the structure of Formula (XIII): R5Rxor a pharmaceuticallyAttorney Docket No.: R2054-7034WO A is C(R’); each of B and D are independently N; wherein A and B or A and D are connected via a double or single bond; each of R1, R2, R5, and R6 are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1- C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano; wherein A and B form a double bond and Rxis hydrogen or wherein A and D form a double bond and Ryis hydrogen; R3 is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, or N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R4; R’ is absent, hydrogen, or C1-C6 alkyl; each R4 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, fluorine, chlorine, bromine, or iodine; RAis hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, or heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; each of RBand RCis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl are each optionally substituted with one or more R7; or wherein RBand RCare taken together to form heterocyclyl optionally substituted with one or more R7; each R7is C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, -ORA, fluorine, chlorine, bromine, iodine, nitro, or cyano.

6. The method of claim 1, wherein the MC4R agonist is a peptide or a small molecule.

7. The method of claim 1, wherein the MC4R agonist is a peptide.Attorney Docket No.: R2054-7034WO 8. The method of claim 1, wherein the MC4R agonist has the structure of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII) or a pharmaceutically acceptable salt thereof, e.g., as described herein.

9. The method of claim 1, wherein the MC4R agonist has the structure of Formula (I), or a pharmaceutically acceptable salt thereof, e.g., as described herein.

10. The method of claim 9, wherein R2is Ac.

11. The method of claim 9, wherein R3is H.

12. The method of claim 9, wherein R1is NH2.

13. The method of claim 9, wherein A1 is Arg.

14. The method of claim 9, wherein A2is Cys.

15. The method of claim 9, wherein A9is Cys.

16. The method of claim 9, wherein A3is deleted.

17. The method of claim 9, wherein A4is His.

18. The method of claim 9, wherein A5is D-(X1, X2, X3, X4, X5)Phe.

19. The method of claim 9, wherein A5is D-Phe.

20. The method of claim 9, wherein A6is Arg.

21. The method of claim 9, wherein A7is Trp.Attorney Docket No.: R2054-7034WO 22. The method of claim 9, wherein A8is deleted.

23. The method of claim 1, wherein the MC4R agonist is: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 140), or a pharmaceutically acceptable salt thereof.

24. The method of claim 1, wherein the MC4R agonist has the structure of Formula (XII), or a pharmaceutically acceptable salt thereof, e.g., as described herein.

25. The method of claim 24, wherein A1is Ac.

26. The method of claim 24, wherein Yyy is Arg.

27. The method of claim 24, wherein Aaa is hCys.

28. The method of claim 24, wherein Xxx is selected from Asn, Gln, Ser, and Thr.

29. The method of claim 24, wherein Bbb is Pen.

30. The method of claim 24, wherein A2is NH2.

31. The method of claim 1, wherein the MC4R agonist is selected from the following structural formulas: Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 629) Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 630) Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 631); and Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 632), or a pharmaceutically acceptable salt thereof.

32. The method of claim 1, wherein the MC4R agonist is:Attorney Docket No.: R2054-7034WO Ac-Arg-c(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 629), or a pharmaceutically acceptable salt thereof.

33. The method of claim 1, wherein the MC4R agonist is: Ac-Arg-c(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 630), or a pharmaceutically acceptable salt thereof.

34. The method of claim 1, wherein the MC4R agonist is: Ac-Arg-c(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 631), or a pharmaceutically acceptable salt thereof.

35. The method of claim 1, wherein the MC4R agonist is: Ac-Arg-c(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2; (SEQ ID NO: 632), or a pharmaceutically acceptable salt thereof.

36. The method of claim 1, wherein the SURx / Kirx channel activator compound is administered at a dosage of between about 1 mg / kg to about 200 mg / kg.

37. The method of claim 1, wherein the SURx / Kirx channel activator compound is administered at a dosage of between about 25 mg / kg to about 125 mg / kg.

38. The method of claim 1, wherein the SURx / Kirx channel activator compound is administered at a dosage of between about 75 mg / kg.

39. The method of claim 1, wherein the MC4R agonist is administered at a dosage of between about 0.5 mg / kg to about 20 mg / kg.

40. The method of claim 1, wherein the MC4R agonist is administered at a dosage of between about 2.5 mg / kg to about 15 mg / kg.Attorney Docket No.: R2054-7034WO 41. The method of claim 1, wherein the MC4R agonist is administered at a dosage of about 5 mg / kg.

42. The method of claim 1, wherein the MC4R agonist is administered at a dosage of about 10 mg / kg.

43. The method of claim 1, wherein the SURx / Kirx channel activator compound is formulated for oral administration.

44. The method of claim 1, wherein the SURx / Kirx channel activator compound is formulated for parenteral administration.

45. The method of claim 1, wherein the SURx / Kirx channel activator compound is formulated for subcutaneous administration.

46. The method of claim 1, wherein the MC4R agonist is administered parenterally.

47. The method of claim 1, wherein the MC4R agonist is administered subcutaneously.

48. The method of claim 1, wherein the MC4R agonist is dosed with a needle (e.g, a 20-25 gauge needle).

49. The method of claim 1, wherein (i) the SURx / Kirx channel activator compound and (ii) the MC4R agonist are administered as a single formulation.

50. The method of claim 1, wherein (i) the SURx / Kirx channel activator compound and (ii) the MC4R agonist are administered as separate formulations.

51. The method of claim 1, wherein (i) the SURx / Kirx channel activator compound is administered orally; and (ii) the MC4R agonist is administered parenterally, e.g., subcutaneously.Attorney Docket No.: R2054-7034WO 52. The method of claim 1, wherein (i) the SURx / Kirx channel activator compound is administered orally once per day; and (ii) the MC4R agonist is administered parenterally, e.g., subcutaneously, once per week.

53. The method of claim 1, wherein the efficacy of the combination is at least X1-fold greater than the efficacy of the SURx / Kirx channel activator compound alone at the molar amount used in the combination, wherein X1is 1, 1.25, 1.5, 1.75, 2, 2.5, or greater.

54. The method of claim 1, wherein the efficacy of the combination is at least X1-fold greater than the efficacy of the MC4R agonist alone at the molar amount used in the combination, wherein X1 is 1, 1.25, 1.5, 1.75, 2, 2.5, or greater.

55. The method of claim 1, wherein the efficacy of the combination is at least X1-fold greater than the efficacy of the SURx / Kirx channel activator compound alone or the MC4R agonist alone at the molar amount used in the combination, wherein X1 is 1, 1.25, 1.5, 1.75, 2, 2.5, or greater.

56. The method of claim 1, wherein the molar amount of the SURx / Kirx channel activator compound in the combination comprises the molar concentration of the SURx / Kirx channel activator compound in the combination.

57. The method of claim 1, wherein the molar amount of the MC4R agonist in the combination comprises the molar concentration of the MC4R agonist in the combination.

58. The method of claim 1, wherein each of the SURx / Kirx channel activator compound and the MC4R agonist is independently formulated as a pharmaceutical composition.

59. The method of claim 1, wherein the SURx / Kirx channel activator compound and the MC4R agonist are formulated together as a pharmaceutical composition.Attorney Docket No.: R2054-7034WO 60. The method of claim 1, wherein the ratio of the amount of SURx / Kirx channel activator compound to the MC4R agonist in the combination is between 200:1 to 1:

1.

61. The method of claim 60, wherein the ratio of the amount of SURx / Kirx channel activator compound to the MC4R agonist in the combination is between 50:1 to 1:

1.

62. The method of claim 60, wherein the ratio of the amount of SURx / Kirx channel activator compound to the MC4R agonist in the combination is between 50:1 to 2:

1.

63. The method of claim 60, wherein the ratio of the amount of SURx / Kirx channel activator compound to the MC4R agonist in the combination is between 25:1 to 2:

1.

64. The method of claim 1, wherein the disease or disorder is obesity.

65. The method of claim 1, wherein the disease or disorder is hypothalamic obesity.

66. The method of claim 1, wherein the disease or disorder is a metabolic syndrome.

67. The method of claim 1, wherein the disease or disorder is Prader-Willi syndrome.

68. The method of claim 1, wherein the disease or disorder is Bardet-Biedl syndrome.

69. The method of claim 1, wherein the disease or disorder is congenital hyperinsulinism (CHI).

70. The method of claim 1, wherein the disease or disorder is a hyperinsulism-related syndrome.

71. The method of claim 1, wherein the disease or disorder is a behavioral disorder or a psychological disorder.