Cleavable ester compounds and uses thereof

Abstract

Provided herein are compounds of formula (I): L— LB-E— D1 (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L, LB, E, and D1 are as defined elsewhere herein. Also provided are methods of preparing a compound of formula (I).

Description

[0001]Attorney Docket No.330272000440 CLEAVABLE ESTER COMPOUNDS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No.63 / 572,077 filed March 29, 2024, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION Aspects of the invention generally relate to a delivery system for active agents to increase the plasma circulation time and duration of the drug in the serum. BACKGROUND OF THE INVENTION The poor pharmacokinetic profile of many drugs represents a major challenge in their continued development. This problem, in particular, has limited the ability of drugs to reach their tremendous therapeutic potential. In particular, the half-life of many drugs in the blood serum of a subject is of serious concern. Short half-life of a drug is usually due to (i) enzymatic degradation by serum proteases and / or (ii) fast renal clearance due to the molecular weight cutoff for peptides and proteins to be cleared through glomerular filtration being relatively high at approximately 30 kilodaltons. Those of skill in the art recognize that the short in vivo half-life of numerous drug candidates has limited their clinical potential by increasing the size and frequencies of doses needed to achieve the desired results, for example. Accordingly, the art will appreciate having a delivery system that (i) improves the duration of action and plasma circulation of active drugs; (ii) avoids steric hindrance problems that affect binding affinity and potency of the active agents; (iii) avoids the renal tubular vacuolation caused by PEGylation; (iv) avoids the generation of antibodies that create immune response problems; and (v) has low manufacturing costs. BRIEF SUMMARY OF THE INVENTION It has been surprisingly discovered that the duration of action (DOA) of a drug can be significantly extended by covalently attaching the drug to a lipid tail or poly(ether) tail through a cleavable linker, wherein the cleavable linker comprises an aromatic moiety (e.g., a para-amino benzoic acid (PABA) moiety or a a para-hydroxybenzoic benzoic acid (PHBA)). Accordingly, the disclosure relates to a fundamentally new prodrug approach for enhancing the plasma circulation and DOA of drugs without affecting their biological activity. ny-2932441 Attorney Docket No.330272000440 In one aspect, provided herein is a compound of formula (I): LLB E D1(I),or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; LBis absent or a click product formed via a Click reaction between a first Click handle and a second click handle; E is a cleavable ester comprising an aromatic moiety; and D1is a drug moiety. The cleavable ester moiety (E) of the compound of formula (I) comprises an aromatic ring. In some embodiments, the aromatic ring can be optionally substituted with one or more substituents as set forth herein. In some embodiments, para-amino benzoic acid (PABA) is used as a basic building block for forming an ester with a drug. In some embodiments, para- hydroxybenzoic benzoic acid (PHBA) is used as a basic building block for forming an ester with a drug moiety. In some embodiments, substituted PABA is used as a basic building block for forming an ester with a drug In some embodiments, the aromatic ester group (e.g., PABA or PHBA) of the compound of formula (I) is hydrolyzed to a greater extent by carboxylesterase 2 (CES2) than by carboxylesterase 1 (CES1). In some embodiments, the aromatic ester group (e.g., PABA or PHBA) of the compound of formula (I) is hydrolyzed by CES2 but only to a minimal extent by CES1. In some embodiments, the aromatic ester group (e.g., PABA) of the compound of formula (I) is fully resistant to CES1. Such CES2 selectivity provides for a more controlled or extended release of the drug from the compound. Additionally, the rate of hydrolysis can be effectively tuned (e.g., increased or decreased) by particular substitutions on the aromatic ester group (e.g., PABA or PHBA group) of the compound. In some embodiments, the compound of formula (I) includes the following ester moiety: ny-2932441 Attorney Docket No.330272000440 wherein represents the point of attachment to L or LB. In some embodiments, the compound of formula (I) includes the following ester moiety: wherein represents the point of attachment to L or LB. R1xis H, F, Cl, NO2, CF3, or OMe, and R1yis H or Me. In some embodiments, R1xis H or Me and R1yis H, F, Cl, Br, NO2, CF3, Me, or OMe. In some embodiments, R1xis H and R1yis Me. In some embodiments, the conjugate of formula (I) includes the following ester moiety: wherein represents the point of attachment to L or LB. In some embodiments, the compound of formula (I) includes the following ester moiety: ny-2932441 Attorney Docket No.330272000440 wherein represents the point of attachment to L or LB. In some embodiments, the compound of formula (I) includes the following ester moiety: wherein represents the point of attachment to L or LB, R1xis H, F, Cl, NO2, CF3, or OMe, and R1yis H or Me. In some embodiments, R1xis H or Me and R1yis H, F, Cl, Br, NO2, CF3, Me, or OMe. In some embodiments, R1xis H and R1yis Me. In one embodiment, provided herein is a compound of formula (II): L is a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; ny-2932441 Attorney Docket No.330272000440 Y2is NR1, O or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, - CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. Any embodiments provided herein of a compound of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, apply where applicable to any other formula detailed herein, the same as if each and every embodiment were specifically and individually listed. Thus, it is understood and described that each embodiment provided herein of a compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, such as embodiments related to L, Y1, Y2, LB, E, R2, p, D1apply to any of formulas (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII) or a pharmaceutically acceptable salt thereof, the same as if each and every embodiment were specifically and individually listed. It is also understood and described that all such embodiments may be used in any of the pharmaceutical compositions, methods, kits, uses, or other aspects detailed herein. In one aspect, provided herein are methods of increasing the plasma circulation time and DOA of a drug, said method comprising administering to a subject (e.g., a human patient) a therapeutically effective amount of a compound of the disclosure (e.g., compound of formula (I) or formula (II)). In some embodiments, administering the compound of the disclosure (e.g., compound of formula (I) or formula (II)) reduces the immunogenicity of the active agent relative to administering the drug alone in free form (nonconjugated form). In some embodiments, a compound of the disclosure is administered parenterally to a subject in need thereof. For instance, a compound of the disclosure can be administered subcutaneously, intravenously, intramuscularly or intrathecally. In other embodiments, the conjugates of the disclosure are administered orally. ny-2932441 Attorney Docket No.330272000440 Release of the active agent can be effectively controlled by proper selection of a cleavable moiety in the compound. For instance, particular ester moieties, as described herein, hydrolyze slowly following administration, thereby releasing the active agent in a controlled manner for an extended period of time. The slower hydrolysis effectively extends the plasma circulation time of the active agent. In some embodiments, D1is a peptide. In some embodiments, the peptide is RGK- MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1- 42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments, the active drug (D1) delivered by a compound of the disclosure is a small molecule, a nucleotide, an oligonucleotide, a polynucleotide, an amino acid, an oligopeptide, a polypeptides, or a proteins. Active drugs can include, but are not limited to, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants. In some embodiments, D1is a peptide, an oligopeptide, a polypeptide, a protein, an antibody, an oligonucleotide, a polynucleotide, a virus-like particle, a small molecule, an oligosaccharide, or an imaging agent. In some embodiments, D1is a protein. In some embodiments, D1is an antibody. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL- 15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments, D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments, D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. ny-2932441 Attorney Docket No.330272000440 In some embodiments, following the administration of a compound of the disclosure (e.g., a compound of formula (I) or formula (II)), the plasma circulation and the duration of action (DOA) of the drug is at least 12 hours. In some such embodiments, following the administration of a compound the disclosure (e.g., a compound of formula (I) or formula (II)), the DOA of the drug is at least 20 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of drug is at least 96 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 1 week. In some embodiments, following the administration of a conjugate of the disclosure, the DOA of the drug is at least 2 weeks. In some embodiments, following the administration of a conjugate of the disclosure, the DOA of the drug is at least 1 month. In some embodiments, the compounds disclosed herein can provide a controlled and / or extended release of a drug. In some such embodiments, slow release of the drug from the compound can be administered safely. In some embodiments, a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.005 mg / kg to about 40 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.01 mg / kg to about 40 mg / kg. In some embodiments. a conjugate of the disclosure is administered subcutaneously to a human subject at a dose of from about 10 mg / kg to about 40 mg / kg. In some embodiments. a conjugate of the disclosure is administered subcutaneously to a human subject at a dose of from about 10 mg / kg to about 20 mg / kg. DETAILED DESCRIPTION OF THE INVENTION Here we developed a fundamentally new prodrug approach for enhancing the DOA of drugs without affecting their biological activity. Our approach involves conjugating the drug through an aromatic ester moiety to a lipid tail or poly(ether) tail. The approach described herein can be used for a variety of drug moieties, including small molecules, peptides and proteins. ny-2932441 Attorney Docket No.330272000440 DEFINITIONS “Individual” or “subject” refers to mammals and includes humans and non-human mammals. Examples of individuals include, but are not limited to, mice, rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs, goats, sheep, cows, monkeys, and humans. In some embodiments, individual or subject refers to a human. As used herein, “about” a parameter or value includes and describes that parameter or value per se. For example, “about X” includes and describes X per se. “Treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. Beneficial or desired results may include one or more of the following: decreasing one or more symptom resulting from the disease or condition; diminishing the extent of the disease or condition; slowing or arresting the development of one or more symptom associated with the disease or condition (e.g., stabilizing the disease or condition, preventing or delaying the worsening or progression of the disease or condition); and relieving the disease, such as by causing the regression of clinical symptoms (e.g., ameliorating the disease state, enhancing the effect of another medication, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival). As used herein, “delaying” development of a disease or condition means to defer, hinder, slow, retard, stabilize and / or postpone development of the disease or condition. This delay can be of varying lengths of time, depending on the history of the disease and / or individual being treated. As is evident to one skilled in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease or condition. As used herein, the term “therapeutically effective amount” or “effective amount” intends such amount of a compound of the disclosure or a pharmaceutically salt thereof sufficient to effect treatment when administered to an individual. As is understood in the art, an effective amount may be in one or more doses, e.g., a single dose or multiple doses may be required to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved. ny-2932441 Attorney Docket No.330272000440 As used herein, “unit dosage form” refers to physically discrete units, suitable as unit dosages, each unit containing a predetermined quantity of active ingredient, or compound, which may be in a pharmaceutically acceptable carrier. As used herein, by “pharmaceutically acceptable” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects. As used herein, the term “half-life” can be used to refer to lose half of its activity, for example, its pharmacologic, physiologic, or radiologic activity. The term “half-life” can be used interchangeably with the terms “biological half-life” or “terminal half-life”. In some embodiments, the half-life of a substance is the time it takes for a substance, for example, a metabolite, drug, signalling molecule, radioactive nuclide, or other substance, to lose half of its pharmacologic, physiologic, or radiologic activity. In some embodiments, the term half- life can be used to refer to the body's cleansing through the function of kidneys and liver in addition to excretion functions to eliminate a substance from the body. In some embodiments, the term “half-life” can be used to refer to the time it takes for the blood plasma concentration of a substance to halve (plasma half-life) its steady-state. As used herein, the term “linker”, “linkage” and “linking group” refers to a chemical linking moiety that connects two groups and has a backbone of 50 atoms or less in length. In some embodiments, the linker or linkage may be a covalent bond that connects two groups, or a chemical moiety having a chain of between 1 and 50 atoms in length, between 2 and 20 atoms in length, between 3 and 30 atoms in length, between 4 and 40 atoms in length, between 10 and 50 atoms in length, between 10 and 30 atoms in length, between 12 and 26 atoms in length, between 14 and 30 atoms in length, or any range therein in amounts of 1 atom in length. For example, a linker or a portion of a linker can have a length that is 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 45, or 50 carbon atoms in length, where the linker may be linear, branched, cyclic, or a single atom. In some embodiments, the linker may be 10 angstroms, 11 angstroms, 12 angstroms, 13 angstroms, 14 angstroms, 15 angstroms, 16 angstroms, 17 angstroms, 18 angstroms, 19 angstroms, 20 angstroms, 22 angstroms, 23 angstroms, 24 angstroms, 25 angstroms, 26 angstroms, 27 angstroms, 28 angstroms, 29 angstroms, 30 angstroms, 32 angstroms, 34 angstroms, 36 angstroms, 38 angstroms, 40 angstroms, 45 angstroms, 50 angstroms, or any amount therein ny-2932441 Attorney Docket No.330272000440 in increments of 1 angstrom, in length. In some embodiments, one, two, three, four or five or more carbon atoms of a linker backbone may be optionally substituted with a sulfur, nitrogen or oxygen heteroatom. The bonds between backbone atoms may be saturated or unsaturated, usually not more than one, two, or three unsaturated bonds will be present in a linker backbone. The linker may include one or more substituent groups, for example with an alkyl, aryl or alkenyl group. A linker may include, without limitations, oligo(ethylene glycol); ethers, thioethers, tertiary amines, alkyls, which may be straight or branched, e.g., methyl, ethyl, n-propyl, 1-methylethyl (iso-propyl), n-butyl, n-pentyl, 1,1-dimethylethyl (t-butyl), and the like. The linker backbone may include a cyclic group, for example, an aryl, a heterocycle or a cycloalkyl group, where 2 or more atoms, e.g., 2, 3 or 4 atoms, of the cyclic group are included in the backbone. A linker may be cleavable or non-cleavable. The term “alkyl”, as used herein, refers to an unbranched or branched saturated univalent hydrocarbon chain. As used herein, alkyl has 1-20 carbons (i.e., C1-20alkyl), 1-16 carbons (i.e., C1-16alkyl), 1-12 carbons (i.e., C1-12alkyl), 1-10 carbons (i.e., C1-10alkyl), 1-8 carbons (i.e., C1-8alkyl), 1-6 carbons (i.e., C1-6alkyl), 1-4 carbons (i.e., C1-4alkyl), or 1-3 carbons (i.e., C1-3alkyl). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, iso-pentyl, neo-pentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “butyl” includes n-butyl, sec-butyl, iso-butyl, and tert-butyl; and “propyl” includes n-propyl and iso- propyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkyl” group, may be referred to as an “alkylene”. The term “alkenyl”, as used herein, refers to a branched or unbranched univalent hydrocarbon chain comprising at least one carbon-carbon double bond. As used herein, alkenyl has 2-20 carbons (i.e., C2-20alkenyl), 2-16 carbons (i.e., C2-16alkenyl), 2-12 carbons (i.e., C2-12alkenyl), 2-10 carbons (i.e., C2-10alkenyl), 2-8 carbons (i.e., C2-8alkenyl), 2-6 carbons (i.e., C2-6alkenyl), 2-4 carbons (i.e., C2-4alkenyl), or 2-3 carbons (i.e., C2-3alkenyl). Examples of alkenyl include, but are not limited to, ethenyl, prop-1-enyl, prop-2-enyl 1,2- butadienyl, and 1,3-butadienyl. When an alkenyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that ny-2932441 Attorney Docket No.330272000440 number of carbon atoms may be encompassed—for example, “propenyl” includes prop-1- enyl and prop-2-enyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkenyl” group, may be referred to as an “alkenylene”. The term “alkynyl”, as used herein, refers to a branched or unbranched univalent hydrocarbon chain comprising at least one carbon-carbon triple bond. As used herein, alkynyl has 2-20 carbons (i.e., C2-20alkynyl), 2-16 carbons (i.e., C2-16alkynyl), 2-12 carbons (i.e., C2-12alkynyl), 2-10 carbons (i.e., C2-10alkynyl), 2-8 carbons (i.e., C2-8alkynyl), 2-6 carbons (i.e., C2-6alkynyl), 2-4 carbons (i.e., C2-4alkynyl), or 2-3 carbons (i.e., C2-3alkynyl). Examples of alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1- ynyl, but-2-ynyl, and but-3-ynyl. When an alkynyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “propynyl” includes prop-1- ynyl and prop-2-ynyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkynyl” group, may be referred to as an “alkynylene”. The term “alkoxy”, as used herein, refers to an -O-alkyl moiety. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy. The term “aryl”, as used herein, refers to a fully unsaturated carbocyclic ring moiety. The term “aryl” encompasses monocyclic and polycyclic fused-ring moieties. As used herein, aryl encompasses ring moieties comprising, for example, 6 to 20 annular carbon atoms (i.e., C6-20aryl), 6 to 16 annular carbon atoms (i.e., C6-16aryl), 6 to 12 annular carbon atoms (i.e., C6-12aryl), or 6 to 10 annular carbon atoms (i.e., C6-10aryl). Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, fluorenyl, and anthryl. The term “cycloalkyl”, as used herein, refers to a saturated or partially unsaturated carbocyclic ring moiety. The term “cycloalkyl” encompasses monocyclic and polycyclic ring moieties, wherein the polycyclic moieties may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl groups, wherein the ring moiety comprises at least one annular double bond. Cycloalkyl includes any polycyclic carbocyclic ring moiety comprising at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As ny-2932441 Attorney Docket No.330272000440 used herein, cycloalkyl includes rings comprising, for example, 3 to 20 annular carbon atoms (i.e., a C3-20cycloalkyl), 3 to 16 annular carbon atoms (i.e., a C3-16cycloalkyl), 3 to 12 annular carbon atoms (i.e., a C3-12cycloalkyl), 3 to 10 annular carbon atoms (i.e., a C3-10cycloalkyl), 3 to 8 annular carbon atoms (i.e., a C3-8cycloalkyl), 3 to 6 annular carbon atoms (i.e., a C3- 6cycloalkyl), or 3 to 5 annular carbon atoms (i.e., a C3-5cycloalkyl). Monocyclic cycloalkyl ring moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norbonyl, decalinyl, 7,7-dimethyl -bicyclo [2.2.1]heptanyl, and the like. Still further, cycloalkyl also includes spiro cycloalkyl ring moieties, for example, spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro [5.5]undecanyl. The term “halo”, as used herein, refers to atoms occupying groups VIIA of The Periodic Table and includes fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodo). Additionally, terms such as “haloalkyl” are meant to include monohaloalkyl and polyhaloalkyl. For example, the term “C1-4haloalkyl” is mean to include trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, difluoromethyl, and the like. The term “heteroaryl”, as used herein, refers to an aromatic (fully unsaturated) ring moiety that comprises one or more annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heteroaryl” includes both monocyclic and polycyclic fused-ring moieties. As used herein, a heteroaryl comprises, for example, 5 to 20 annular atoms (i.e., a 5- to 20-membered heteroaryl), 5 to 16 annular atoms (i.e., a 5- to 16-membered heteroaryl), 5 to 12 annular atoms (i.e., a 5- to 12-membered heteroaryl), 5 to 10 annular atoms (i.e., a 5- to 10-membered heteroaryl), 5 to 8 annular atoms (i.e., a 5- to 8-membered heteroaryl), or 5 to 6 annular atoms (i.e., a 5- to 6-membered heteroaryl). Any monocyclic or polycyclic aromatic ring moiety comprising one or more annular heteroatoms is considered a heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heteroaryl moiety). Examples of heteroaryl groups include, but are not limited to, oxazolyl, thiazolyl, pyridinyl, pyrimidinyl, and pyridazinyl. The term “heterocyclyl”, as used herein, refers to a saturated or partially unsaturated cyclic moiety that encompasses one or more annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heterocyclyl” includes ny-2932441 Attorney Docket No.330272000440 both monocyclic and polycyclic ring moieties, wherein the polycyclic ring moieties may be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic ring moiety comprising at least one annular heteroatom is considered a heterocyclyl, regardless of the point of attachment to the remainder of the molecule (i.e., the heterocyclyl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heterocyclyl moiety). Further, the term heterocyclyl is intended to encompass any polycyclic ring moiety comprising at least one annular heteroatom wherein the polycyclic ring moiety comprises at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, a heterocyclyl comprises, for example, 3 to 20 annular atoms (i.e., a 3- to 20-membered heterocyclyl), 3 to 16 annular atoms (i.e., a 3- to 16- membered heterocyclyl), 3 to 12 annular atoms (i.e., a 3- to 12-membered heterocyclyl), 3 to 10 annular atoms (i.e., a 3- to 10-membered heterocyclyl), 3 to 8 annular atoms (i.e., a 3- to 8-membered heterocyclyl), 3 to 6 annular atoms (i.e., a 3- to 6-membered heterocyclyl), 3 to 5 annular atoms (i.e., a 3- to 5-membered heterocyclyl), 5 to 8 annular atoms (i.e., a 5- to 8- membered heterocyclyl), or 5 to 6 annular atoms (i.e., a 5- to 6-membered heterocyclyl). Examples of heterocyclyl groups include, e.g., azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrofuryl, or tetrahydropyranyl. Examples of spiro heterocyclyl rings include, but are not limited to, bicyclic and tricyclic ring systems, such as oxabicyclo[2.2.2]octanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6- azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of fused heterocyclyl rings include, but are not limited to, 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidinyl, 6,7-dihydro- 5H-pyrrolo[3,4-d]pyrimidinyl, 5,7-dihydrofuro[3,4-d]pyrimidinyl, and 5,7-dihydrothieno[3,4- d]pyrimidinyl, where the heterocyclyl can be bound via either ring of the fused system. The term “oxo”, as used herein, refers to a =O moiety. The terms “optional” and “optionally”, as used herein, mean that the subsequently described event or circumstance may or may not occur and that the description includes instances where the event or circumstance occurs and instances where it does not. Accordingly, the term “optionally substituted” infers that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms on the designated atom or moiety or group may be replaced or not replaced by an atom or moiety or group other than hydrogen. By way of illustration and not limitation, the phrase “methyl optionally substituted with one or more chloro” encompasses -CH3, -CH2Cl, -CHCl2, and -CCl3moieties. ny-2932441 Attorney Docket No.330272000440 It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments. The term “pharmaceutically acceptable salt”, as used herein, of a given compound refers to salts that retain the biological effectiveness and properties of the given compound and which are not biologically or otherwise undesirable. “Pharmaceutically acceptable salts” include, for example, salts with inorganic acids, and salts with an organic acid. In addition, if the compounds described herein are obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, may be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. See, e.g., Handbook of Pharmaceutical Salts Properties, Selection, and Use, International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), which is incorporated herein by reference in its entirety. Those skilled in the art will recognize various synthetic methodologies that may be used to prepare nontoxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts may be prepared from inorganic or organic acids. Salts derived from inorganic acids include, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include, e.g., acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluene-sulfonic acid, salicylic acid, trifluoroacetic acid, and the like. Likewise, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, aluminum, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines. Specific examples of suitable amines include, by way of example only, isopropylamine, trimethyl amine, diethyl amine, tri(iso-propyl) amine, tri(n-propyl) amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N- ethylpiperidine, and the like. Isotopically labeled forms of the compounds depicted herein may be prepared. Isotopically labeled compounds have structures depicted herein, except that one or more ny-2932441 Attorney Docket No.330272000440 atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,13N,15N,15O,17O,18O,31P,32P,35S,18F,36Cl,123I, and125I, respectively. In some embodiments, a compound of formula (I) is provided wherein one or more hydrogen is replaced by deuterium or tritium. Some of the compounds provided herein may exist as tautomers. Tautomers are in equilibrium with one another. By way of illustration, amide containing compounds may exist in equilibrium with imidic acid tautomers. Regardless of which tautomer is shown and regardless of the nature of the equilibrium among tautomers, the compounds of this disclosure are understood by one of ordinary skill in the art to comprise both amide and imidic acid tautomers. Thus, for example, amide-containing compounds are understood to include their imidic acid tautomers. Likewise, imidic-acid containing compounds are understood to include their amide tautomers. The compounds of the present disclosure, or their pharmaceutically acceptable salts, may include an asymmetric center and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- (or as (D)- or (L)- for amino acids). The present disclosure is meant to include all such possible isomers, as well as their racemic and optically pure forms and mixtures thereof in any ratio. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or may be resolved using conventional techniques, for example, chromatography and / or fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or the resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC), and chiral supercritical fluid chromatography (SFC). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, unless specified otherwise, it is intended that the present disclosure includes both E and Z geometric isomers. Likewise, cis- and trans- are used in their conventional sense to describe relative spatial relationships. COMPOUNDS In one aspect, provided herein is a compound of formula (I): ny-2932441 Attorney Docket No.330272000440 LLB E D1(I),or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; LBis absent or a click product formed via a Click reaction between a first Click handle and a second click handle; E is a cleavable ester comprising an aromatic moiety; and D1is a drug moiety. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of about 10 Å to about 50 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of from about 15 Å to about 45 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of from about 25 Å to about 40 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of about 20 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of about 25 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of about 30 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of about 35 Å. In some embodiments, the lipid tail or poly(ether) tail (L) and click product (LB) taken together have a size of about 40 Å. In some embodiments, LBis the Click product of: (i) a copper-catalyzed reaction between an azide and an alkyne; (ii) a reaction between an azide and dibenzocyclooctene (DBCO); (iii) an inverse electron demand Diels-alder cycloaddition (IEDDA) between a trans- cyclooctene (TCO) moiety and a tetrazine ring, or (iv) a Staudinger reaction between an azide and a phosphine. In some embodiments, the first click handle and the second click handle used to form click product LBcan be any suitable click chemistry pair (e.g., Azide-DBCO, Azide-BCN, ny-2932441 Attorney Docket No.330272000440 Tz-TCO, meTz-TCO, etc.). In some embodiments, the click product can be formed using a copper-catalyzed click reaction. One such copper-catalyzed click reaction is a Huisgen 1,3- dipolar cycloaddition (CuAAC) between an azide and an alkyne (see, e.g., Tornøe et al., J. Org. Chem.2002, 67 (9), 3057-3064 and Rostovtsev et al., Angew. Chem. Int. Ed.2002, 41 (14), 2596-2599). In some embodiments, the click product is a triazole moiety. In some embodiments, the click product can be formed using a biorthogonal chemistry approach. In some embodiments, the click product LBcan be formed from any suitable inverse electron demand Diels-Alder reaction. In some embodiments, the click product can be formed from an inverse electron demand Diels-Alder reaction between a trans-cyclooctene (TCO) moiety on the first or second click handle and a tetrazine (Tz) ring on the first or second click handle (see, e.g., Selvaraj et al., Curr. Opin. Chem. Biol.2013, 17 (5), 753-760 and Rossin et al., Bioconjugate Chem.2013, 24 (7), 1210-1217). In some embodiments, the first click handle comprises a tetrazine ring and the second click handle comprises a TCO moiety. In some embodiments, the tetrazine ring is unsubstituted. In some such embodiments, the tetrazine ring is methyltetrazine. In some embodiments, the tetrazine ring is a 6-methyl substituted tetrazine. In some embodiments, the click product is a dihydropyridazine moiety. In some embodiments, the click product LBis a triazine moiety. In some embodiments, the compound of formula (I) comprises one of the following moieties: , wherein X2is -CH2-, -NRx-, -S- or -O-, wherein Rxis defined as elsewhere herein. In some embodiments, the compound comprises the moiety In some embodiments, the compound comprises the moiety . In some embodiments, the click product LBis an octahydrocyclooctapyridazine moiety. In some embodiments, the compound of formula (I) comprises the moiety ny-2932441 Attorney Docket No.330272000440 , wherein LB1is H or C1-4 alky1. In some embodiments, the compound comprises the moiety alky1. In some embodiments, L is linear C4-100alkyl, wherein the linear C4-100alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and - S-. In some embodiments, L is linear C4-20alkyl, wherein the linear C4-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, L is linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, L is linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted ny-2932441 Attorney Docket No.330272000440 with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments, L is unsubstituted linear C4-100alkyl. In some embodiments, L is unsubstituted linear C4-50alkyl. In some embodiments, L is unsubstituted linear C4-20alkyl. In some embodiments, L is unsubstituted linear C10-20alkyl. In some embodiments, L is unsubstituted linear C10-15alkyl. In some embodiments, L is unsubstituted linear C5-10alkyl. In some embodiments, L is a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with L1a. In some embodiments, L is wherein n is an integer between 2 and 30. In some embodiments, L iswherein n is an integer between 4 and 20. In some embodiments, L iswherein n is an integer between 4 and 15. In some embodiments, L iswherein n is an integer between 4 and 10. In some embodiments, L iswherein n is an integer between 2 and 10. In some embodiments, L is , wherein n is an integer between 2 and 5.In some embodiments, each L1ais halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, -C(O)NH(RL), -C(O)N(RL)2, -P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, - OH, or -NH2. In some embodiments, each L1ais halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1-6alkyl)NH2, -C(O)NH2, -C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, -C(O)OH, -C(O)O(C1-4alkyl), -C(O)(C1-4alkyl)NH2, - C(O)NH2, -C(O)NH(C1-4alkyl), -C(O)N(C1-4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, -CH3, -CH2H3, -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, - CH2H2F, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, - C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or ny-2932441 Attorney Docket No.330272000440 oxo. In some embodiments, each L1ais halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, - C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, - C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, - C(O)OH, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, - P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, -C(O)OH, - C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments, L comprises the moiety some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety some embodiments, L comprises the moiety ny-2932441 Attorney Docket No.330272000440 moiety . In some embodiments, L comprises the moiety . In some embodiments, L-LBcomprises the moiety . In some L-LBcomprises the moiety . In some embodiments, L-LBcomprises the moiety . In some embodiments, L-LBcomprises the moiety some embodiments, L-LBcomprises the moiety embodiments, L-LBcomprises the moiety some embodiments, L-LBcomprises the moiety ny-2932441 Attorney Docket No.330272000440 embodiments, L-LBcomprises the moiety In some embodiments, L-LBcomprises the moiety In some embodiments, the compound of formula (I) comprises the moiety ny-2932441 Attorney Docket No.330272000440 Ring A is C6-10aryl or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more R7, wherein each R7is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NO2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, -CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl and indicates the point of attachment to the lipid tail or poly(ether) tail (L or L-LB). In some embodiments, Ring A is an optionally substituted 5- to 10-membered heteroaryl. Examples of heteroaryl rings include, but are not limited to, azetidinyl, pyrazyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, pyridazyl, indolizyl, isoindolyl, indolyl, dihydroindolyl, indazolyl, purinyl, quinolizinyl, isoquinolinyl, quinolinyl, phthalazinyl, naphthylpyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, carbolinyl, phenanthridinyl, acridinyl, phenanthrolinyl, isothiazolyl, phenazinyl, isoxazolyl, phenoxazinyl, phenothiazinyl, imidazolidinyl, imidazolinyl, piperidinyl, piperazinyl, indolinyl, phthalimidyl, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrobenzo[b]thiophenyl, thiazolyl, thiazolidinyl, thiophenyl, benzo[b]thiophenyl, morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, pyrrolidinyl, and tetrahydrofuranyl. In some embodiments, Ring A is selected from the group consisting of phenyl, pyridyl, pyrimidinyl, oxazolyl, pyrazolyl, and thiazolyl, wherein the phenyl, pyridyl, pyrimidinyl, oxazolyl, pyrazolyl, or thiazolyl is optionally substituted with one or more C1-6alkyl, C1-6alkoxy, hydroxy, halo, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, - CONH2, -CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C3-6cycloalkyl, or -NO2, ny-2932441 Attorney Docket No.330272000440 wherein the C1-6 alkyl or C1-6 alkoxy is optionally substituted by one or more halo. In some embodiments, Ring A is selected from the group consisting of phenyl, pyridyl, and pyrimidinyl, wherein the phenyl, pyridyl, and pyrimidinyl is optionally substituted with one or more C1-6 alkyl, C1-6 alkoxy, hydroxy, halo, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, -CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C3-6 cycloalkyl, or nitro, wherein the C1-6 alkyl or C1-6 alkoxy is optionally substituted by one or more halo. In some embodiments, Ring A is a phenyl group or a substituted phenyl group. In some such embodiments, Ring A is substituted with a methyl group, methoxy group, halo group (e.g., Cl, Br, F or I), nitro group, or CF3group. In some embodiments, the conjugate of formula (I) comprises the moiety is In some embodiments, the compound of formula (I) comprises the moiety is In some embodiments, the compound of formula (I) comprises the moiety ny-2932441 Attorney Docket No.330272000440 each R7is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6alkoxy and C3-6cycloalkyl, p is 0, 1, 2, or 3, and indicates the point of attachment to the lipid tail or poly(ether) tail (L or L-LB). In some embodiments, the compound of formula (I) comprises the moiety ny-2932441 Attorney Docket No.330272000440 wherein: Ring A is C6-10aryl or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more R7, wherein each R7is independentlyselected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, - N(C1-4alkyl)2, -CONH2, -CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6 alkoxy and C3-6 cycloalkyl; and indicates the point of attachment to the lipid tail or poly(ether) tail (L). In some embodiments, the compound of formula (I) comprises the moiety wherein each R7is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6alkoxy and C3-6cycloalkyl, p is 0, 1, 2, or 3, and indicates the point of attachment to the lipid tail or poly(ether) tail (L). In some embodiments, the compound of formula (I) comprises the moiety ny-2932441 Attorney Docket No.330272000440 , In some embodiments, the compound of formula (I) comprises the moiety , wherein each methylene group can be optionally substituted with halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, -CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy or C3-6 cycloalkyl. In some embodiments, the compound of formula (I) comprises the moiety wherein each methylene group can be optionally substituted with halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, -CONHC1-4 alkyl, - CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy or C3-6 cycloalkyl. and wherein indicates the point of attachment to the lipid tail or poly(ether) tail (L or L- LB), wherein indicates the point of attachment to the lipid tail or poly(ether) tail (L). In some embodiments, the compound of formula (I) comprises the moiety ny-2932441 Attorney Docket No.330272000440 lipid tail or poly(ether) tail (L). In some embodiments, D is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to treat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist used to treat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic ny-2932441 Attorney Docket No.330272000440 extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments, D is a protein. In some embodiments, D is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL- 15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1 is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments, D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments, D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In one embodiment, provided herein is a compound of formula (II’): or a pharmaceutically acceptable salt thereof, wherein: ny-2932441 Attorney Docket No.330272000440 L is a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; Y2is NR1, O or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. In one embodiment, provided herein is a compound of formula (II): or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; Y2is NR1, O or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, - CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. In some embodiments, the compound of formula (II) has the formula (IIa): ny-2932441 Attorney Docket No.330272000440 or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (II) has the formula (IIb): or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (II) has the formula (IIc): (IIc), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (II) has the formula (IId): or a pharmaceutically acceptable salt thereof. In some embodiments of the compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments of the compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), L is linear C4-100alkyl, wherein the linear C4-100alkyl is ny-2932441 Attorney Docket No.330272000440 optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and - S-. In some embodiments, L is linear C4-20alkyl, wherein the linear C4-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, L is linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, L is linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments of the compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), L is unsubstituted linear C4-100alkyl. In some embodiments, L is unsubstituted linear C4-50alkyl. In some embodiments, L is unsubstituted linear C4-20alkyl. In some embodiments, L is unsubstituted linear C10-20alkyl. In some embodiments, L is unsubstituted linear C10-15alkyl. In some embodiments, L is unsubstituted linear C5-10alkyl. In some embodiments of the compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), L is a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with L1a. In some embodiments, L is ,wherein n is an integer between 2 and 30. In some embodiments, L isny-2932441 Attorney Docket No.330272000440 wherein n is an integer between 4 and 20. In some embodiments, L iswherein n is an integer between 4 and 15. In some embodiments, L iswherein n is an integer between 4 and 10. In some embodiments, L iswherein n is an integer between 2 and 10. In some embodiments, L is , wherein n is an integer between 2 and 5.In some embodiments of the compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), each L1ais halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1- 6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, -C(O)NH(RL), -C(O)N(RL)2, - P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, -OH, or -NH2. In some embodiments, each L1ais halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1-6alkyl)NH2, -C(O)NH2, - C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, -C(O)OH, -C(O)O(C1-4alkyl), - C(O)(C1-4alkyl)NH2, -C(O)NH2, -C(O)NH(C1-4alkyl), -C(O)N(C1-4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, -CH3, -CH2H3, -CF3, -CHF2, -CH2F, -CH2CF3, - CH2CHF2, -CH2H2F, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, - C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, - C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, - C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, - C(O)OH, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, - P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, -C(O)OH, - C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments of the compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), L comprises the moiety.ny-2932441 Attorney Docket No.330272000440 In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety embodiments, L comprises the moiety . In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety some embodiments, L comprises the moiety . In some embodiments, L comprises the moiety some embodiments, L comprises the moiety moiety . In some embodiments of a compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), D1is a protein. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In ny-2932441 Attorney Docket No.330272000440 one such embodiment, the IL-15 is IL-15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments of a compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), D1is an anti-cancer agent. In some such embodiments, D1is SN- 38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (II) or (II’), or any variation thereof, such as formula (IIa)-(IId), D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In one embodiment, provided herein is a compound of formula (III’): or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; LBis a click product formed via a Click reaction between a first Click handle and a second click handle; Y1is a bond or C1-4alkylene; Y2is NR1, O, or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - ny-2932441 Attorney Docket No.330272000440 CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. In one embodiment, provided herein is a compound of formula (III): or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; LBis a click product formed via a Click reaction between a first Click handle and a second click handle; Y1is a bond or C1-4alkylene; Y2is NR1, O, or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, - CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. In some embodiments, the compound of formula (III) has the formula (IIIa): or a pharmaceutically acceptable salt thereof. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the compound of formula (III) has the formula (IIIb): or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (III) has the formula (IIIc): or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (III) has the formula (IIId): or a pharmaceutically acceptable salt thereof. In some embodiments of the compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments of the compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), LAis linear C4-100alkyl, wherein the linear C4-100alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and - S-. In some embodiments, LAis linear C4-20alkyl, wherein the linear C4-20alkyl is optionally ny-2932441 Attorney Docket No.330272000440 substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments of the compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), LAis unsubstituted linear C4-100alkyl. In some embodiments, LAis unsubstituted linear C4-50alkyl. In some embodiments, LAis unsubstituted linear C4-20alkyl. In some embodiments, LAis unsubstituted linear C10-20alkyl. In some embodiments, LAis unsubstituted linear C10-15alkyl. In some embodiments, LAis unsubstituted linear C5-10alkyl. In some embodiments of the compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), LAis a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with LA1. In some embodiments, LAis , wherein n is an integer between 2 and 30. In some embodiments, LAis, wherein n is an integer between 4 and 20. In some embodiments, LAis, wherein n is an integer between 4 and 15. In someny-2932441 Attorney Docket No.330272000440 embodiments, LAis, wherein n is an integer between 4 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 5.In some embodiments of the compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1- 6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, -C(O)NH(RL), -C(O)N(RL)2, - P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, -OH, or -NH2. In some embodiments, each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1-6alkyl)NH2, -C(O)NH2, - C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, -C(O)OH, -C(O)O(C1-4alkyl), - C(O)(C1-4alkyl)NH2, -C(O)NH2, -C(O)NH(C1-4alkyl), -C(O)N(C1-4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, -CH3, -CH2H3, -CF3, -CHF2, -CH2F, -CH2CF3, - CH2CHF2, -CH2H2F, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, - C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, - C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, - C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, - C(O)OH, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, - P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -C(O)OH, - C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments of the compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety embodiments, LAcomprises the moiety . In some ny-2932441 Attorney Docket No.330272000440 embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety some embodiments, LAcomprises the moiety . In some LA moiety . In some embodiments, LA comprises the moiety . In some embodiments, LAcomprises the moiety embodiments, LAcomprises the moiety In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), the click product LBis a triazine moiety. In some embodiments, the compound of formula (III), or any variation thereof, such as formula (IIIa)- (IIId), comprises one of the following moieties: , wherein X2is -CH2-, - NRx-, -S- or -O-, wherein Rxis as defined elsewhere herein. In some embodiments, the compound comprises the moiety . In some embodiments, the compound comprises the moiety . ny-2932441 Attorney Docket No.330272000440 In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), the click product LBis an octahydrocyclooctapyridazine moiety. In some embodiments, the compound of formula (III), or any variation thereof, such as formula (IIIa)-(IIId), comprises the moiety wherein LB1is H or C1-4alky1. In some embodiments, the compound comprises the moiety wherein LB1is H or C1-4 alky1. In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), LA-LBcomprises the moiety LA-LBcomprises the moiety . In some embodiments, LA-LBcomprises the moiety some embodiments, LA-LBcomprises the moiety ny-2932441 Attorney Docket No.330272000440 some embodiments, LA-LBcomprises the moiety LA-LB. In some embodiments, LA-LBcomprises the moiety some embodiments, LA-LBcomprises the moiety embodiments, LA-LBcomprises the moiety In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), LA-LBcomprises the moiety In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), D1is a protein. In some embodiments, D1is a cytokine. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL-15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL- 9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL- 10). In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide ny-2932441 Attorney Docket No.330272000440 drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (III) or (III’), or any variation thereof, such as formula (IIIa)-(IIId), D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In some embodiments, provided herein is a compound of formula (IV’): or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; Y2is NR6, O or S; ny-2932441 Attorney Docket No.330272000440 R6is H or C1-4alkyl; each R7is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6alkoxy and C3-6cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. In some embodiments, provided herein is a compound of formula (IV): or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; Y2is NR6, O or S; R6is H or C1-4alkyl; each R7is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, - CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6alkoxy and C3-6cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety. In some embodiments, the compound of formula (IV) has the formula (IVa): or a pharmaceutically acceptable salt thereof. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the compound of formula (IV) has the formula (IVb): or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (IV) has the formula (IVc): or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (IV) has the formula (IVd): or a pharmaceutically acceptable salt thereof. In some embodiments of the compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments of the compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), LAis linear C4-100alkyl, wherein the linear C4-100alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and - S-. In some embodiments, LAis linear C4-20alkyl, wherein the linear C4-20alkyl is optionally ny-2932441 Attorney Docket No.330272000440 substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments of the compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), LAis unsubstituted linear C4-100alkyl. In some embodiments, LAis unsubstituted linear C4-50alkyl. In some embodiments, LAis unsubstituted linear C4-20alkyl. In some embodiments, LAis unsubstituted linear C10-20alkyl. In some embodiments, LAis unsubstituted linear C10-15alkyl. In some embodiments, LAis unsubstituted linear C5-10alkyl. In some embodiments of the compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), LAis a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with LA1. In some embodiments, LAis , wherein n is an integer between 2 and 30. In some embodiments, LAis, wherein n is an integer between 4 and 20. In some embodiments, LAis, wherein n is an integer between 4 and 15. In someny-2932441 Attorney Docket No.330272000440 embodiments, LAis , wherein n is an integer between 4 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 5.In some embodiments of the compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1- 6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, -C(O)NH(RL), -C(O)N(RL)2, - P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, -OH, or -NH2. In some embodiments, each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1-6alkyl)NH2, -C(O)NH2, - C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, -C(O)OH, -C(O)O(C1-4alkyl), - C(O)(C1-4alkyl)NH2, -C(O)NH2, -C(O)NH(C1-4alkyl), -C(O)N(C1-4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, -CH3, -CH2H3, -CF3, -CHF2, -CH2F, -CH2CF3, - CH2CHF2, -CH2H2F, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, - C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, - C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, - C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, - C(O)OH, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, - P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -C(O)OH, - C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments of the compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some ny-2932441 Attorney Docket No.330272000440 embodiments, LAcomprises the moiety In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some A embodiments, L comprises the moiety . In some A embodiments, L comprises the moiety . In some embodiments, LAcomprises the moiety . In some LA moiety . In some embodiments, LA comprises the moiety . In some embodiments, LAcomprises the moiety embodiments, LAcomprises the moiety In some embodiments of a compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), D1is a protein. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL-15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL- 9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the ny-2932441 Attorney Docket No.330272000440 cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL- 10). In some embodiments of a compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (IV) or (IV’), or any variation thereof, such as formula (IVa)-(IVd), D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In some embodiments, provided herein is a compound of formula (V): or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; Z1is C6-10aryl or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety. In some embodiments of the compound of formula (V), L is linear C4-100alkyl, wherein the linear C4-100alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some ny-2932441 Attorney Docket No.330272000440 embodiments, L is linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C4-20alkyl, wherein the linear C4-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, L is linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, L is linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, L is linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more L1a, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments of the compound of formula (V), L is unsubstituted linear C4- 100alkyl. In some embodiments, L is unsubstituted linear C4-50alkyl. In some embodiments, L is unsubstituted linear C4-20alkyl. In some embodiments, L is unsubstituted linear C10-20alkyl. In some embodiments, L is unsubstituted linear C10-15alkyl. In some embodiments, L is unsubstituted linear C5-10alkyl. In some embodiments of the compound of formula (V), L is a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with L1a. In some embodiments, L is, wherein n is an integer between 2 and 30. In some embodiments, L is, wherein n is an integer between 4 and 20. Inny-2932441 Attorney Docket No.330272000440 some embodiments, L is, wherein n is an integer between 4 and 15. In some embodiments, L is, wherein n is an integer between 4 and 10. In some embodiments, L is, wherein n is an integer between 2 and 10. In some embodiments, L is, wherein n is an integer between 2 and 5.In some embodiments of the compound of formula (V), each L1ais halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, -C(O)NH(RL), -C(O)N(RL)2, -P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, -OH, or -NH2. In some embodiments, each L1ais halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1- 6alkyl)NH2, -C(O)NH2, -C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, -C(O)OH, -C(O)O(C1-4alkyl), -C(O)(C1-4alkyl)NH2, -C(O)NH2, -C(O)NH(C1-4alkyl), -C(O)N(C1- 4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, -CH3, -CH2H3, -CF3, - CHF2, -CH2F, -CH2CF3, -CH2CHF2, -CH2H2F, hydroxy, -OCH3, -OCH2H3, -C(O)OH, - C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, - C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, -C(O)OH, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, - C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each L1ais halo, hydroxy, - C(O)OH, -C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments of the compound of formula (V), L comprises the moiety . In some L ny-2932441 Attorney Docket No.330272000440 . In some L . In some L . In some L comprises the moiety . In some embodiments, L comprises the moiety In some embodiments of a compound of formula (V), or any variation thereof, D1is a protein. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL- 15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). ny-2932441 Attorney Docket No.330272000440 In some embodiments of a compound of formula (V), or any variation thereof, D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (V), or any variation thereof, D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic ny-2932441 Attorney Docket No.330272000440 extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (V), or any variation thereof, D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (V), or any variation thereof, D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In some embodiments, provided herein is a compound of formula (VI): or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; LBis a click product formed via a Click reaction between a first Click handle and a second click handle; Z1is C6-10aryl, or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis independently halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety. In some embodiments of the compound of formula (VI), LAis linear C4-100alkyl, wherein the linear C4-100alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group ny-2932441 Attorney Docket No.330272000440 selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C4-20alkyl, wherein the linear C4-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments of the compound of formula (VI), LAis unsubstituted linear C4- 100alkyl. In some embodiments, LAis unsubstituted linear C4-50alkyl. In some embodiments, LAis unsubstituted linear C4-20alkyl. In some embodiments, LAis unsubstituted linear C10- 20alkyl. In some embodiments, LAis unsubstituted linear C10-15alkyl. In some embodiments, LAis unsubstituted linear C5-10alkyl. In some embodiments of the compound of formula (VI), LAis a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with LA1. In some embodiments, LA is, wherein n is an integer between 2 and 30. In some embodiments, LAis, wherein n is an integer between 4 and 20. In some embodiments, LAis, wherein n is an integer between 4 and 15. Inny-2932441 Attorney Docket No.330272000440 some embodiments, LAis, wherein n is an integer between 4 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 5.In some embodiments of the compound of formula (VI), each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, - C(O)NH(RL), -C(O)N(RL)2, -P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, -OH, or -NH2. In some embodiments, each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1- 6alkyl)NH2, -C(O)NH2, -C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, - C(O)OH, -C(O)O(C1-4alkyl), -C(O)(C1-4alkyl)NH2, -C(O)NH2, -C(O)NH(C1-4alkyl), - C(O)N(C1-4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, -CH3, - CH2H3, -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, -CH2H2F, hydroxy, -OCH3, -OCH2H3, - C(O)OH, -C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, - C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, - C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -C(O)OH, -C(O)CH2NH2, -C(O)NH2, - C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -C(O)OH, -C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments of the compound of formula (VI), LAcomprises the moiety . In some LAny-2932441 Attorney Docket No.330272000440 . In some moiety . In some embodiments, LAcomprises the moiety In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some embodiments, LA comprises the moiety . In some embodiments, LAcomprises the moiety embodiments, LAcomprises the moiety In some embodiments of a compound of formula (VI), the click product LBis a triazine moiety. In some embodiments, the compound of formula (VI), comprises one of the following moieties: , wherein X2is -CH2-, -NRx-, -S- or -O-, wherein Rxis as defined elsewhere herein. In some embodiments, the compound comprises the moiety ny-2932441 Attorney Docket No.330272000440 In some embodiments of a compound of formula (VI), the click product LBis an octahydrocyclooctapyridazine moiety. In some embodiments, the compound of formula (VI), comprises the moiety wherein LB1is H or C1-4alky1. In some embodiments, the compound comprises the moiety wherein LB1is H or C1-4 alky1. In some embodiments of a compound of formula (VI), LA-LBcomprises the moiety . In some embodiments, LA-LBcomprises the moiety LA-LBcomprises the moiety . In some embodiments, LA-LBcomprises the moiety some embodiments, LA-LBcomprises the moiety some embodiments, LA-LBcomprises the moiety ny-2932441 Attorney Docket No.330272000440 LA-LB. In some embodiments, LA-LBcomprises the moiety some embodiments, LA-LBcomprises the moiety embodiments, LA-LBcomprises the moiety In some embodiments of a compound of formula (VI), LA-LBcomprises the moiety In some embodiments of a compound of formula (VI), or any variation thereof, D1is a protein. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In ny-2932441 Attorney Docket No.330272000440 some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL- 15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments of a compound of formula (VI), or any variation thereof, D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (VI), or any variation thereof, D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the ny-2932441 Attorney Docket No.330272000440 disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (VI), or any variation thereof, D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (VI), or any variation thereof, D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In some embodiments, provided herein is a compound of formula (VII): or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; Z1is C6-10aryl, or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety. ny-2932441 Attorney Docket No.330272000440 In some embodiments of the compound of formula (VII), LAis linear C4-100alkyl, wherein the linear C4-100alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C4-50alkyl, wherein the linear C4-50alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C4-20alkyl, wherein the linear C4-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-20alkyl, wherein the linear C10-20alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, -N(CH3)-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C10-15alkyl, wherein the linear C10-15alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NH-, and -N(CH3)-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, -NRx-, and -S-. In some embodiments, LAis linear C5-10alkyl, wherein the linear C5-10alkyl is optionally substituted with one or more LA1, and one or more alkylene units is optionally replaced with a group selected from -O-, and -NH-. In some embodiments of the compound of formula (VII), LAis unsubstituted linear C4-100alkyl. In some embodiments, LAis unsubstituted linear C4-50alkyl. In some embodiments, LAis unsubstituted linear C4-20alkyl. In some embodiments, LAis unsubstituted linear C10-20alkyl. In some embodiments, LAis unsubstituted linear C10-15alkyl. In some embodiments, LAis unsubstituted linear C5-10alkyl. In some embodiments of the compound of formula (VII), LAis a poly(ethylene glycol) moiety of 30 or fewer repeat units, wherein one or more alkylene units are substituted with LA1. In some embodiments, LAis, wherein n is an integer between 2ny-2932441 Attorney Docket No.330272000440 and 30. In some embodiments, LAis , wherein n is an integer between 4 and 20. In some embodiments, LAis, wherein n is an integer between 4 and 15.CH3O In some embodiments, LAisn , wherein n is an integer between 4 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 10. In some embodiments, LAis, wherein n is an integer between 2 and 5.In some embodiments of the compound of formula (VII), each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)ORL, -C(O)(RL), -C(O)NH2, - C(O)NH(RL), -C(O)N(RL)2, -P(O)(OH)2, or oxo, wherein each RLis independently C1-6alkyl optionally substituted by one or more halo, -OH, or -NH2. In some embodiments, each LA1is halo, C1-6alkyl, C1-6haloalkyl, hydroxy, C1-6alkoxy, -C(O)OH, -C(O)O(C1-6alkyl), -C(O)(C1-6alkyl)NH2, -C(O)NH2, -C(O)NH(C1-6alkyl), -C(O)N(C1-6alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, - C(O)OH, -C(O)O(C1-4alkyl), -C(O)(C1-4alkyl)NH2, -C(O)NH2, -C(O)NH(C1-4alkyl), - C(O)N(C1-4alkyl)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, -CH3, - CH2H3, -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, -CH2H2F, hydroxy, -OCH3, -OCH2H3, - C(O)OH, -C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, -C(O)NH2, -C(O)NHCH3, - C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -OCH3, -OCH2H3, -C(O)OH, -C(O)OCH3, -C(O)OCH2H3, -C(O)CH2NH2, - C(O)NH2, -C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -C(O)OH, -C(O)CH2NH2, -C(O)NH2, - C(O)NHCH3, -C(O)NHCH2H3, -C(O)N(CH3)2, -P(O)(OH)2, or oxo. In some embodiments, each LA1is halo, hydroxy, -C(O)OH, -C(O)CH2NH2, -P(O)(OH)2, or oxo. In some embodiments of the compound of formula (VII), LAcomprises the moiety ny-2932441 Attorney Docket No.330272000440 . In some O . In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety . In some embodiments, LAcomprises the moiety In some embodiments, LAcomprises the embodiments, LAcomprises the moiety embodiments, LAcomprises the moiety In some embodiments of a compound of formula (VII), or any variation thereof, D1is a protein. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL- 15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is ny-2932441 Attorney Docket No.330272000440 Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments of a compound of formula (VII), or any variation thereof, D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (VII), or any variation thereof, D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (VII), or any variation thereof, D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (VII), or any variation thereof, D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In some embodiments, provided herein is a compound of formula (VIII): or a pharmaceutically acceptable salt thereof, wherein: Z1is C6-10aryl or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety. In some embodiments of the compound of formula (VIII), or any variation thereof, n is an integer between 2 and 30. In some embodiments, n is an integer between 4 and 20. In some embodiments, n is an integer between 4 and 15. In some embodiments, n is an integer ny-2932441 Attorney Docket No.330272000440 between 4 and 10. In some embodiments, n is an integer between 2 and 10. In some embodiments, n is an integer between 2 and 5. In some embodiments, n is 4. In some embodiments of a compound of formula (VIII), or any variation thereof, D1is a protein. In some embodiments, D1is a cytokine. In some embodiments, the cytokine is Interleukin-2 (IL-2). In some embodiments, the cytokine is mutated IL-2, such as a cytokine described in US 9,206,943. In some embodiments, the cytokine is Interleukin-15 (IL-15). In some embodiments, the cytokine is mutated IL-15. In one such embodiment, the IL-15 is IL- 15[N27D]. In some embodiments, the cytokine is Interleukin-7 (IL-7). In some embodiments, the cytokine is Interleukin-9 (IL-9). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments, the cytokine is Interleukin-21 (IL-21). In some embodiments, the cytokine is Interleukin-10 (IL-10). In some embodiments of a compound of formula (VIII), or any variation thereof, D1is an anti-cancer agent. In some such embodiments, D1is SN-38. In some such embodiments, D1is monomethyl auristatin E. In some such embodiments, D1is capecitabine. In some such embodiments, D1is irinotecan. In some such embodiments, D1is trifluridine. In some such embodiments, D1is doxorubicin. In some such embodiments, D1is docetaxel. In some such embodiments, D1is infigratinib. In some embodiments of a compound of formula (VIII), or any variation thereof, D1is a peptide. In some embodiments, the peptide is RGK-MCA. In some embodiments, the peptide is Neurotensin. In some embodiments, the peptide is Gonadotropin-releasing hormone (GnRH). In some embodiments, the peptide is GIP (1-42), human peptide. In some embodiments, the peptide is D6-GnRH. In some embodiments, the peptide is insulin. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is calcitronin salmon. In some embodiments, the peptide is ipamorelin. In some embodiments, the peptide is vasopressin. In some embodiments, the peptide is glucagon. In some embodiments, the peptide is aclerastide. In some embodiments, the peptide is goserelin. In some embodiments, the peptide is leuprolide. In some embodiments, the peptide is teriparatide. In some embodiments, the peptide is lixisenatide. In some embodiments, the peptide is desmopressin. In some embodiments, the peptide is oxytocin. In some embodiments, the peptide is corticotropin. In some embodiments, the peptide is sermorelin. ny-2932441 Attorney Docket No.330272000440 In some embodiments, the peptide is bremelanotide. In some embodiments, the peptide is abaloparatide. In some embodiments, the peptide is deslorelin. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) receptor agonist used to trat obesity and / or diabetes. In some such embodiments the peptide drug is semaglutide, liraglutide, dulaglutide, albiglutide, or exenatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide drug is a glucagon-like-peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide receptor agonist used to trat obesity and / or diabetes. In some such embodiments, the peptide drug is tirzepatide. Owing to the dramatic extension of duration of action of peptide drugs when incorporated into the conjugates of the disclosure, the GLP-1 / GIP agonist conjugates can be administered on a reduced dosing schedule, such as once weekly, once biweekly, once every three weeks, or once monthly. In some embodiments, the peptide is an endogenous opioid peptide. In some such embodiments, the peptide is endomorphin-1 or endomorphin-2. In other embodiments, the peptide is dermorphin. In some embodiments of a compound of formula (VIII), or any variation thereof, D1is an opioid antagonist. In some embodiments, the opioid antagonist is naloxone, nalmefene, naltrexone, methylnaltrexone, nalbuphine, or nalorphine. In some embodiments of a compound of formula (VIII), or any variation thereof, D1is an opioid agonist. In some embodiments, the opioid agonist is morphine, oxycodone, hydromorphone, or methadone. In some embodiments, provided herein is a compound with a structure as shown: , wherein D1is defined as elsewhere herein. In some embodiments, provided herein is a compound with a structure as shown: ny-2932441 Attorney Docket No.330272000440 wherein D1is defined as elsewhere herein. In some embodiments, provided herein is a compound with a structure as shown: In some embodiments, provided herein is a compound with a structure as shown: In some embodiments, provided herein is a compound with a structure as shown: In some embodiments, provided herein is a compound with a structure as shown: ny-2932441 Attorney Docket No.330272000440 In some embodiments, provided herein is a compound with a structure as shown: In some embodiments, provided herein is a compound with a structure as shown: PHARMACEUTICAL COMPOSITIONS Provided herein are pharmaceutical compositions comprising one or more compounds of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, as described elsewhere herein, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, provided herein is a pharmaceutical composition comprising (i) a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, as described elsewhere herein, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. Suitable pharmaceutically acceptable excipients may include, for example, fillers, diluents, sterile aqueous solutions and various organic solvents, permeation enhancers, solubilizers, and adjuvants. Various substances may be embraced by the term excipient, including without limitation any substance used as a binder, disintegrant, coating, compression / encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspending / gelling agent, or wet granulation agent. Examples of suitable excipients are well-known to those skilled in the art. See, e.g., Handbook of Pharmaceutical Excipients, Pharmaceutical Press ny-2932441 Attorney Docket No.330272000440 (2017), which is incorporated herein by reference in its entirety. Such compositions are prepared in a manner well known in the pharmaceutical art. See, e.g., Remington’s Pharmaceutical Sciences, Academic Press, 23rded. (2020), which is incorporated herein by reference in its entirety. METHODS OF TREATMENT In one aspect, provided herein are methods of increasing the plasma circulation time of an active agent, comprising covalently attaching an active agent to a lipid tail or poly(ether) tail to form a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In one aspect, provided herein are methods of increasing the in vivo half-life of an active agent,, comprising covalently attaching an active agent to a lipid tail or poly(ether) tail to form a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In one aspect, provided herein are methods of increasing the duration of action (DOA) of an active agent, comprising covalently attaching an active agent to a lipid tail or poly(ether) tail to form a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In one aspect, provided herein are methods of treating a disease, disorder, or condition comprising administering to an individual in need thereof a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a ny-2932441 Attorney Docket No.330272000440 stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. In some embodiments, a therapeutically effective amount of the compound is administered. In some embodiments, the half-life of the activity of the active agent can range from about 30 minutes to about 90 days when administered to a subject with the delivery systems provided herein. In some embodiments, the half-life of the activity of the active agent can range from about 30 minutes to about 30 days when administered to a subject with the delivery systems provided herein. In some embodiments, the half-life of the activity of the active agent can be about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 12 hours, about 18 hours, about 24 hours, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 10 days, about 12 days, about 16 days, about 20 days, about 30 days, or any amount therein in increments of 1 hour, when administered to a subject with a delivery system taught herein. One of skill will appreciate that the half-life of the activity of an active agent that is administered to a subject using a delivery system taught herein can range from about 30 minutes to about 2 days, from about 1 hour to about 36 hours, from about 2 hours to about 20 hours, from about 2 hours to about 10 hours, from about 3 hours to about 30 hours, from about 3 hours to about 15 hours, from about 4 hours to about 40 hours, from about 4 hours to about 20 hours, from about 5 hours to about 50 hours, from about 5 hours to about 25 hours, or any range or any amount therein in increments of 1 hour. In one aspect, provided herein are methods of reducing the risk of recurrent respiratory depression, comprising administering to an individual in need thereof a compound of the disclosure prior to exposure to a drug. In one aspect, provided herein are methods of prophylaxis, comprising administering to an individual in need thereof a compound of the disclosure prior to exposure to a drug. In some embodiments, a compound of the disclosure is administered parenterally to a subject in need thereof. For instance, a compound of the disclosure can be administered subcutaneously, intravenously, intramuscularly or intrathecally. Moreover, it has been discovered that release of the active agent can be effectively controlled by proper selection of a cleavable moiety in the compound. For instance, ny-2932441 Attorney Docket No.330272000440 particular ester moieties (e.g., PABA or PHBA), as described herein, hydrolyze slowly following administration, thereby releasing the active agent in a controlled manner for an extended period of time. The slower hydrolysis effectively extends the plasma circulation time of the active agent. In some embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 12 hours. In some embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 20 hours. In some embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 24 hours. In some embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 30 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 40 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 48 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 72 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 96 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 1 week. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 2 weeks. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 3 weeks. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is at least 1 month. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is from about 12 hours to about 48 hours. In some such embodiments, following the administration of a compound of the disclosure, the DOA of the drug is from about 24 hours to about 48 hours. In some embodiments, following the administration of a compound of the disclosure, the DOA of the drug is from about 48 hours to about 96 hours. In some embodiments, following the administration of a compound of the disclosure, the DOA of the drug is from about 24 hours to about 1 week. In some embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 12 hours. In some embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least ny-2932441 Attorney Docket No.330272000440 20 hours. In some embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 24 hours. In some embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 30 hours. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 40 hours. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 48 hours. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 72 hours. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 96 hours. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 1 week. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 2 weeks. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 3 weeks. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is at least 1 month. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is from about 12 hours to about 48 hours. In some such embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is from about 24 hours to about 48 hours. In some embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is from about 48 hours to about 96 hours. In some embodiments, following the administration of a compound of the disclosure, the plasma circulation of the drug is from about 24 hours to about 1 week. In some embodiments, the active drug (D1) delivered by a compound of the disclosure is a small molecule, a nucleotide, an oligonucleotide, a polynucleotide, an amino acid, an oligopeptide, a polypeptides, or a proteins. Active drugs, include. can include, but are not limited to, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants. Antiproliferatives include, for example, actinomycin D, actinomycin IV, actinomycin I1, actinomycin X1, actinomycin C1, and dactinomycin (Cosmegen.RTM., Merck & Co., Inc.). Antineoplastics or antimitotics include, for example, paclitaxel (TAXOL, Bristol-Myers ny-2932441 Attorney Docket No.330272000440 Squibb Co.), docetaxel (TAXOTERE, Aventis S.A.), methotrexate, irinotecan, SN-38, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (ADRIAMYCIN, Pfizer, Inc.) and mitomycin (MUTAMYCIN, Bristol-Myers Squibb Co.), and any prodrugs, codrugs, metabolites, analogs, homologues, congeners, derivatives, salts and combinations thereof. Antiplatelets, anticoagulants, antifibrin, and antithrombins include, for example, sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro- arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb / IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors (ANGIOMAX, Biogen, Inc.), and any prodrugs, codrugs, metabolites, analogs, homologues, congeners, derivatives, salts and combinations thereof. Cytostatic or antiproliferative agents include, for example, angiopeptin, angiotensin converting enzyme inhibitors such as captopril (CAPOTEN and CAPOZIDE, Bristol-Myers Squibb Co.), cilazapril or lisinopril (PRINVIL and PRINZIDE, Merck & Co., Inc.); calcium channel blockers such as nifedipine; colchicines; fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid); histamine antagonists; lovastatin (MEVACOR, Merck & Co., Inc.); monoclonal antibodies including, but not limited to, antibodies specific for Platelet-Derived Growth Factor (PDGF) receptors; nitroprusside; phosphodiesterase inhibitors; prostaglandin inhibitors; suramin; serotonin blockers; steroids; thioprotease inhibitors; PDGF antagonists including, but not limited to, triazolopyrimidine; and nitric oxide, and any prodrugs, codrugs, metabolites, analogs, homologues, congeners, derivatives, salts and combinations thereof. Antiallergic agents include, but are not limited to, pemirolast potassium (ALAMAST, Santen, Inc.), and any prodrugs, codrugs, metabolites, analogs, homologues, congeners, derivatives, salts and combinations thereof. In some embodiments, D1is selected from the group consisting of ny-2932441 Attorney Docket No.330272000440 In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.005 mg / kg to about 40 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.01 mg / kg to about 40 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.005 mg / kg to about 10 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.1 mg / kg to about 10 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 0.5 mg / kg to about 10 mg / kg. In some embodiments, a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 5 mg / kg to about 40 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 10 mg / kg to about 30 mg / kg. In some embodiments. a compound of the disclosure is administered subcutaneously to a human subject at a dose of from about 15 mg / kg to about 25 mg / kg. KITS The present disclosure further provides kits for carrying out the methods disclosed herein. The kits may comprise a compound or pharmaceutically acceptable salt thereof as described herein and suitable packaging. The kits may comprise one or more containers comprising any compound described herein. In one aspect, a kit includes a compound of the disclosure or a pharmaceutically acceptable salt thereof, and a label and / or instructions for use of the compound in the treatment of a disease or disorder described herein. The kits may comprise a unit dosage form of the compound. ny-2932441 Attorney Docket No.330272000440 Provided herein is a kit, comprising (i) a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients and (ii) instructions for use in treating an individual in need thereof. In some embodiments, the individual is a human. Articles of manufacture are also provided, wherein the article of manufacture comprises a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in a suitable container. In some embodiments, the container may be a vial, jar, ampoule, preloaded syringe, or intravenous bag. METHODS OF PREPARING Provided herein are processes of preparing a compound of any of formulas (I), (II’), (II), (IIa), (IIb), (IIc), (IId), (III’), (III), (IIIa), (IIIb), (IIIc), (IIId), (IV’), (IV), (IVa), (IVb), (IVc), (IVd), (V), (VI), (VII), or (VIII), or any variation or embodiment thereof, or a pharmaceutically acceptable salt of any of the foregoing. The following synthetic methods, along with those that are detailed in the Examples, are merely illustrative of some of the methods by which the compounds of the present disclosure, or an embodiment or aspect thereof, can be synthesized. Various modifications to these synthetic reaction schemes can be made, as will be apparent to those of ordinary skill in the art. Although certain exemplary embodiments are depicted and described herein, the compounds of the present disclosure, or any variation or embodiment thereof, may be prepared using appropriate starting materials according to the methods described generally herein and / or by methods available to one of ordinary skill in the art. ny-2932441 Attorney Docket No.330272000440 When a specific stereoisomer, or an unspecified stereoisomer, or a mixture of stereoisomers is shown in the following general procedures, it is understood that similar chemical transformations can be performed on other specific stereoisomers, or an unspecified stereoisomer, or mixtures thereof. Where specific reagents or solvents are specified for reactions in the general procedures, the skilled artisan will recognize that other reagents or solvents can be substituted as desired. ny-2932441 Attorney Docket No.330272000440 EXAMPLES The following synthetic reaction schemes, which are detailed in the Examples, are merely illustrative of some of the methods by which the compounds of the present disclosure, or an embodiment or aspect thereof, can be synthesized. Various modifications to these synthetic reaction schemes can be made, as will be apparent to those of ordinary skill in the art. The starting materials and the intermediates of the synthetic reaction schemes can be isolated and purified if desired using conventional techniques, including, but not limited to, filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectral data. Although certain exemplary embodiments are depicted and described herein, the compounds of the present disclosure, or any variation or embodiment thereof, may be prepared using appropriate starting materials according to the methods described generally herein and / or by methods available to one of ordinary skill in the art. All publication, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entireties, to the same extent as if each were incorporated by reference individually. Example 1: Synthesis and Characterization of Conjugates of the Disclosure Materials and Methods Materials and reagents. Naloxone hydrochloride (#N285000) was purchased from Toronto Research Chemicals, Toronto, Ontario. Nalmefene hydrochloride (#408550) was purchased from Tocris Bioscience^. Naloxone-D5100 µg / mL (#N-063) was purchased from Cerilliant. Morphine sulfate (CII) (#M1167) and Fentanyl citrate (CII) (#F1147) were purchased from Spectrum Chemical Manufacturing Corporation. Digitonin (#D0540) and Loperamide hydrochloride (# L0154) were purchased from Fisher Scientific. Dodecyl azide (#A1887) was purchased from Synthonix. Prealbumin from human plasma (human TTR) (#P1742) and human serum (#H4522) were purchased from Sigma Aldrich. Innovative grade US origin rat plasma (#IGRTSDPLANAH), rabbit plasma (#IGRBPLANAH), monkey cynomolgus plasma (#IGMNCYPLANAH) and pooled human plasma (#IPLAWBNAH) ny-2932441 Attorney Docket No.330272000440 were purchased from Innovative Research. XTreme 200 Mixed gender human liver microsomes (#1910096), Male IGS SD rat liver microsomes (#2210274), Male cynomolgus monkey liver microsomes (#2210248), and NADPH RapidStart Regeneration System for Extended Metabolism (#K5100-5) were purchased from Xenotech. Human carboxylesterase 1 (CES1, #E0287-1VL) and carboxylesterase 2 (CES2, #C4749) were purchased from Sigma Aldrich. RPMI-1640 Medium and minimum Eagle’s medium (HyClone, Utah, USA), fetal bovine serum (Gemini), penicillin / streptomycin (100 unit / mL and 100 µg / mL (Gibco, NY, USA) and L-Glutamine (Glutamax-100X, #35-050-061, Gibco, NY, USA) were bought from the companies mentioned in the parentheses. CellBIND® 96- well clear plates (#CLS3340- 50EA) were purchased from Corning®. CellTiter 96 non-radioactive cell proliferation assay kit (#G4000, Promega, WI, USA) was used to perform the MTT (3-(4, 5-dimethylthiazol- 2- yl)-2, 5 diphenyltetrazolium bromide) assay for the test compounds in the cell lines. Chemical synthesis and HPLC purity analysis Chemistry general procedures. All reactions were carried out under an argon or nitrogen atmosphere using dry solvents under anhydrous conditions, unless otherwise noted. The solvents used were ACS grade from Fisher. Yields refer to chromatographically and spectroscopically (1H NMR and13C NMR) homogeneous materials, unless otherwise noted. Reagents were purchased from Aldrich and Fisher and used without further purification. Reactions were monitored by thin-layer chromatography (TLC) carried out on EMD Millipore® silica gel 60 plastic TLC plates coated with fluorescent indicator F254TLC (#1.05735.0001), using UV light and iodine chamber as visualizing agents. Normal phase flash column chromatography was carried out using Combi Flash® Rf+ Lumen instrument (Teledyne ISCO) with High Performance Silica Flash Column (RediSep® Rf+ Gold), and preparative thin-layer chromatography (PTLC) separations were carried out on Analtech® 2mm (60F-254) (#P02015).1H NMR and13C NMR spectra were recorded on a JEOL JNM−ECA 600 spectrometer and calibrated using residual undeuterated solvent as an internal reference. High-resolution mass spectra (HRMS) were performed at the mass spectrometry facility at UC Berkley using electrospray ionization from solution. Coupling constants (J) were expressed in Hertz. Preparative HPLC method for purification of the synthesized compounds. The purification was performed on a Waters 150Q LC System w / PDA and FlexInject system ny-2932441 Attorney Docket No.330272000440 connected to a photodiode array detector operating between the UV ranges of 190-800 nm, using Waters Chromesope V2.1 software. The HPLC analysis was performed on an SunFire® Prep C18 OBD Column (19x250 mm, 5 ^m) at ambient temperature upon injection of 5 mL of each sample to obtain the chromatogram at 310 nm UV absorbance. The mobile phase was composed of solvent A consisting of methanol-water (5:95, v / v) containing 0.1% trifluoroacetic acid and solvent B consisting of methanol-water (95:5, v / v) containing 0.1% trifluoroacetic acid and delivered at a flow of 20 mL min-1. The HPLC program was an isocratic gradient for the first 4 min at 0% solvent B followed by a linear increase from 0- 100% solvent B from 4-20 min followed by isocratic elution at 100% solvent B until 24 min followed by linearly going back down to 0% B at 26 min and then remaining at 0% solvent B for 4 min. Analytical HPLC method for evaluating the purity of the synthesized compounds. Detailed HPLC information of key compounds (traces, retention times, and % purity) are included below. The analysis of the key compounds’ purity (>95% for all compounds) was performed using C18 reverse-phase HPLC columns on Arc Premier Waters module HPLC system connected to a Waters 2998 photodiode array detector operating between the UV ranges of 190-800 nm and quantified using the Empower 3 software. The HPLC analysis was performed on a Waters^ XBridge C18 column (4.6x250 mm, 5^m), eluting at 1 mL min-1, at ambient temperature upon injection of 20 ^L of each sample to obtain the chromatogram at 310 nm UV absorbance. The mobile phase was composed of solvent A consisting of methanol-water (5:95, v / v) containing 0.1% ammonium hydroxide and solvent B consisting of methanol-water (95:5, v / v) containing 0.1% ammonium hydroxide. The HPLC program for the C18 column was a gradient method increasing linearly from 0-100 % solvent B at 0-20 min, followed by isocratic elution at 100% solvent B until 25 min, going back down to 0% of B at 27 min, and then remaining at 0% of B for 3 min. General Procedure B. Synthesis of esters To the selected drug (D1), a solution of the selected carboxylic acid (1.2 eq.) and a catalytic amount of an acylation catalyst (e.g., 4-dimethylaminopyridine, 0.2 eq.) dissolved in dichloromethane was added under an inert atmosphere (e.g., N2 or argon). The reaction ny-2932441 Attorney Docket No.330272000440 mixture was stirred for a short period to allow pre-activation, followed by the addition of a coupling reagent such as N,N'-dicyclohexylcarbodiimide (approximately 1 eq.). The reaction mixture was stirred at ambient temperature for an extended period (e.g., 12–24 hrs) to ensure complete conversion. The mixture was then filtered and the solvent was removed under reduced pressure. The crude product was purified using chromatographic techniques (e.g., flash column chromatography on silica gel using an appropriate gradient of ethyl acetate and hexane) to afford the target ester. The structure and purity of the product were confirmed using analytical methods such as nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). General Procedure C. Copper(I)-Catalyzed Azide–Alkyne Cycloaddition (CuAAC). The click (CuAAC) coupling was carried out by coupling naloxone-alkyne / drug- alkyne (1.2 equivalent), azide-linker-AG10 / azide linker (1 equivalent), CuSO4.5H2O (0.5 equivalent), and sodium ascorbate (1.2 equivalent) in a mixture of tetrahydrofuran / water (2:1). The reaction mixture was stirred at room temperature overnight. The tetrahydrofuran and water were removed under reduced pressure. The residues were either purified by silica gel chromatography or were dissolved in methanol and purified by preparative reverse phase HPLC to afford the desired product. General Procedure D. Removal of Boc protecting groups Boc-protected and conjugates and precursors were treated with a mixture of dichloromethane / trifluoroacetic acid (3:1). The reaction mixture was stirred at room temperature for 2 hr under inert atmosphere. Next, ammonium hydroxide dissolved in water (28-36%) was added slowly dropwise along with methanol. This solution was then concentrated under reduced pressure and purified by preparative reverse phase HPLC to afford the desired products. General Procedure E. Fmoc peptide synthesis Rink amide resin was first swollen in dichloromethane (DCM) to prepare it for peptide synthesis. The Fmoc protecting group was removed using 20% piperidine in DMF for 25 minutes, followed by thorough washing with DMF. Coupling was carried out by preactivating the Fmoc-protected amino acid (3 equivalents) with HBTU (3 equivalents) and ny-2932441 Attorney Docket No.330272000440 DIPEA (6 equivalents) in DMF for 3 minutes before adding the mixture to the resin and agitating for 40 minutes. Coupling and Fmoc deprotection were monitored using the Kaiser test to ensure completion. Upon completion of the synthesis, global cleavage from the resin and removal of acid-labile protecting groups (such as t-Boc and t-Bu) were achieved using a cocktail of 95% trifluoroacetic acid (TFA), 2.5% water, and 2.5% triisopropylsilane (TIPS) for 2 hours at room temperature. The crude peptide / peptide ester conjugate was then precipitated with cold diethyl ether, collected by centrifugation, washed, and dried. The final product was purified using preparative HPLC. Synthesis of C12-L-E2-Naloxone Scheme 3 shows a schematic of the synthesis of C12-E2-Naloxone Scheme 3. Synthesis of C12-E2-Naloxone. (4aS,7aR,12bS)-3-allyl-4a-hydroxy-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12- methanobenzofuro[3,2-e]isoquinolin-9-yl 4-(((1-dodecyl-1H-1,2,3-triazol-4- yl)methyl)amino)benzoate (C12-E2-Naloxone). The click (CuAAC) coupling was carried reacting compound 2 (500 mg, 0.86 mmol, 1 equiv), Dodecyl azide (182 mg, 0.85 mmol, 1 equiv), CuSO4.5H2O (106.7 mg, 0.425 mmol, 0.5 equiv), and sodium ascorbate (169.4 mg, 0.855 mmol, 1 equiv) in a 3 mL mixture of THF / H2O (4:1). The reaction mixture was stirred at room temperature overnight. The solution was concentrated under reduced pressure. The residue was extracted by ethyl acetate. The organic extract was concentrated under reduced pressure to afford an intermediate and was used for the next step directly. Then, to a solution of the intermediate, was added a mixture containing TFA and CH2Cl2, (1:4 ratio) (1 mL), and the reaction mixture was stirred at room temperature for 2 hr. The solution was concentrated under reduced pressure and purified by preparative HPLC to afford compound C12-E2- Naloxone. (255 mg, 43% yield over two steps);1H NMR (600 MHz, CD3OD) ^ 7.87-7.78 (m, ny-2932441 Attorney Docket No.330272000440 3H), 6.94 (t, 1H, J = 8.4 ), 6.85-6.78 (m, 1H), 6.61 (s, 2H), 5.91-5.79 (m, 1H), 5.64-5.52 (m, 2H), 4.82 (s, 1H), 4.58-4.34 (m, 1H), 4.27 (t, 2H, J = 7.2 ), 3.92-3.66 (m, 2H), 3.57-3.32 (m, 2H), 3.17-2.50 (m, 3H), 2.21-1.46 (m, 9H), 1.26-1.06 (m, 18H), 0.79 (t, 3H, J = 7.2);13C- NMR (150 MHz, CD3OD) ^ 206.56, 164.97, 148.36, 133.63, 133.04, 131.95, 128.21, 127.65, 126.50, 125.52, 125.30, 124.27, 123.05, 120.21, 119.64, 111.58, 97.09, 93.49, 89.43, 69.73, 62.55, 55.47, 50.14, 49.02, 46.31, 33.42, 31.73, 29.89, 29.39, 29.19, 28.69, 27.59, 26.97, 26.08, 25.41, 24.73, 22.93, 22.40, 13.12; HRMS (DART) m / z: calcd for C41H53N5O5[M+H]+696.4119; found: 696.4121. Synthesis of PEG Linker-E2-Naloxone PEG-Linker-E2-Naloxone was prepared according to General Procedure B using followed by General Procedure C using , followed by General Procedure D. Analytical HPLC method. Test compounds were analyzed using Waters^ XBridge C18 column (4.6x250 mm, 5 ^m) on Arc Premier Waters module HPLC system connected to a Waters 2998 photodiode array detector operating between the UV ranges of 190-800 nm. HPLC analysis was performed using a gradient method increasing linearly from 0-100% solvent B in 25 min. The mobile phase was composed of solvent A consisting of methanol- water (5:95, v / v) containing 0.1% ammonium hydroxide and solvent B consisting of methanol-water (95:5, v / v) containing 0.1% ammonium hydroxide, at a flow rate of 1.0 mL min-1. ny-2932441 Attorney Docket No.330272000440 Solubility of compounds in potassium phosphate buffer (pH 7.4). Stocks solutions (10 mM) of test compounds were prepared in DMSO and stored at -20°C. Compounds (100 µM) were incubated in 50 mM potassium phosphate buffer (pH 7.4) at 37oC for 72 hr. The samples were vortexed, spun for 5 min at 12000 rpm, and supernatant was filtered. A sample aliquot (100 µL) was then removed and quenched by adding 200 µL of 0.1% formic acid in methanol. The mixture was centrifuged again at 12000^rpm for 5^minutes. Clear supernatant was then analyzed by analytical HPLC as described method. Calibration curves for prodrugs were generated by dissolving DMSO solution of test compounds in 0.1% formic acid in methanol (concentrations at 100, 50, 25, 12.5, and 6.25 µM) and then analyzed by HPLC. Calibration curves were used to quantitate the concentration of soluble test compounds in the potassium phosphate buffer. Data represent the mean ± s.d. (n = 3 independent replicates) and a representative HPLC trace is shown. Log D7.4 determination using shake-flask. An aqueous potassium phosphate buffer (10 mM, pH 7.4) solution has been prepared and then saturated with n-octanol. Likewise, n- octanol was saturated with the pH 7.4 potassium aqueous phosphate buffer. Both solutions have been heavily vortexed and then left resting to ensure complete separation of the two phases. The shake-flask experiments were carried out at room temperature. Once the phases have been prepared, 1 mL of 1-octanol and 1 mL of the aqueous potassium phosphate buffer are added to a glass vial.20 µL of test compound stock solution (10 mM stock solution in DMSO; 100 µM final concentration in the pre-saturated mixture) is added and the vial is shaken for one hour at room temperature. After one hour, the layers were allowed to separate and aliquots (100 µL) of each of the n-octanol and aqueous buffer layers were processed by adding 200 µL of 0.1% formic acid in methanol. The mixture was centrifuged again at 12,000^rpm for 5^minutes. Clear supernatant was then analyzed by analytical HPLC as described method. Calibration curves were used to quantitate the concentration of test compounds. Data represent the mean ± s.d. (n = 3 independent replicates). The following equation was used to calculate Log D7.4. ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^ ^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ny-2932441 Attorney Docket No.330272000440 Example 2: Stability Analysis Human stability assay of test compounds. Test compounds (5 ^M) were incubated in human plasma at 37°C.100 ^L plasma samples were analyzed at 0 hr, 0.25 hr, 2 hr, 4 hr, and 24 hr. All the samples were processed by adding 200 ^L of quenching buffer (0.1% formic acid in methanol) followed by centrifuging at 15,000 rpm for 5 minutes. The supernatant was kept in the -20°C freezer for 5 minutes and centrifuged again at 15,000 rpm for another 5 minutes. The supernatant was analyzed by analytical HPLC as described method. Data represent the mean ± s.d. (n = 3 independent replicates). Results: We evaluated the stability of the prodrugs in human plasma. The following compounds, referred to as HD15, was tested for stability C12-E2-naloxone was fully protected from hydrolysis in human plasma after 4 hours. Minimal hydrolysis (less than 10%) was observed after 24 hours. HD15 was fully protected from hydrolysis in human plasma after 4 hours. Minimal hydrolysis (approximately 15%) was observed after 24 hours. Next, we evaluated whether the PABA group alone was sufficient to stabilize the compounds from hydrolysis by enzymes in human plasma. The following compound, referred to as HD3, was tested for stability. ny-2932441 Attorney Docket No.330272000440 HD3 was only partially protected from hydrolysis after 4 hours. About 60% of the drug was intact after 40 hours. After 24 hours, less than 10% of the drug remained. Accordingly, the presence of both a hydrolysable aromatic ester (e.g., PABA) and lipid tail or poly(ether) tail renders the drugs highly resistant to hydrolysis in human plasma. ny-2932441

Claims

Attorney Docket No.330272000440 CLAIMS What is claimed is:

1. A compound of formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; LBis absent or a click product formed via a Click reaction between a first Click handle and a second click handle; E is a cleavable ester comprising an aromatic moiety; and D1is a drug moiety.

2. The compound of claim 1, wherein: LBis the Click product of: (i) a copper-catalyzed reaction between an azide and an alkyne; (ii) a reaction between an azide and dibenzocyclooctene (DBCO); (iii) an inverse electron demand Diels-alder cycloaddition (IEDDA) between a trans- cyclooctene (TCO) moiety and a tetrazine ring, or (iv) a Staudinger reaction between an azide and a phosphine.

3. The compound of claim 1, wherein L is , wherein n is an integer between 2 and 30 4. The compound of claim 3, wherein n is an integer between 4 and 10.

5. The compound of claim 3, wherein n is an integer between 2 and 5 ny-2932441Attorney Docket No.330272000440 6. A compound of formula (II’):or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; Y2is NR1, O or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6alkoxy and C3-6cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety.

7. A compound of formula (III’):or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; LBis a click product formed via a Click reaction between a first Click handle and a second click handle; Y1is a bond or C1-4alkylene; Y2is NR1, O, or S; R1is H or C1-4alkyl; each R2is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, -CONH2, - CONHC1-4 alkyl, -CON(C1-4 alkyl)2, -NHCOC1-4 alkyl, C1-6 alkyl, C1-6 alkoxy and C3-6 cycloalkyl; ny-2932441Attorney Docket No.330272000440 p is 0, 1, 2, or 3; and D1is drug moiety.

8. A compound of formula (IV’):or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; Y1is a bond or C1-4alkylene; Y2is NR6, O or S; R6is H or C1-4alkyl; each R7is independently selected from the group consisting of hydrogen, halogen atoms (e.g., Cl, Br or F), hydroxy, -OCF3, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2, -CONH2, - CONHC1-4alkyl, -CON(C1-4alkyl)2, -NHCOC1-4alkyl, C1-6alkyl, C1-6alkoxy and C3-6cycloalkyl; p is 0, 1, 2, or 3; and D1is drug moiety.

9. A compound of formula (V):or a pharmaceutically acceptable salt thereof, wherein: L is a lipid tail or poly(ether) tail; Z1is C6-10aryl or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety. ny-2932441Attorney Docket No.330272000440 10. A compound of formula (VI):or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; LBis a click product formed via a Click reaction between a first Click handle and a second click handle; Z1is C6-10aryl, or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis independently halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety.

11. A compound of formula (VII):or a pharmaceutically acceptable salt thereof, wherein: LAis a lipid tail or poly(ether) tail; Z1is C6-10aryl, or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety.

12. A compound of formula (VIII):or a pharmaceutically acceptable salt thereof, wherein: Z1is C6-10aryl or 5- to 10-membered heteroaryl, wherein the C6-10aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Z1b; each Z1bis halo, C1-6alkoxy, or C1-6alkyl optionally substituted by halo; and D1is drug moiety. ny-2932441Attorney Docket No.330272000440 13. A compound that has the structure:, wherein D1is a drug moiety.

14. The conjugate of any one of claims 1-13, wherein D1is a peptide.

15. The conjugate of any one of claims 1-13, wherein D1is a small molecule, a nucleotide, an oligonucleotide, a polynucleotide, an amino acid, an oligopeptide, a polypeptides, or a protein.

16. The conjugate of any one of claims 1-13, wherein D1is a cytokine.

17. The conjugate of claim 16, wherein the cytokine is Interleukin-2 (IL-2).

18. The conjugate of claim 16, wherein the cytokine is Interleukin-15 (IL-15).

19. The conjugate of any one of claims 1-13, wherein D1is an anti-cancer agent.

20. The conjugate of claim 19, wherein the anti-cancer agent is SN-38, irinotecan, capecitabine, monomethyl auristatin E, trifluridine, docetaxel, or infigratinib.

21. The conjugate of anyone of claims 1-13, wherein D1is insulin.

22. A method of treating a disease, comprising administering a conjugate if any one of claims 1-21.

23. The method of claim 22, further comprising administering a second drug (D2) in free (unconjugated) form.

24. The method of claim 23, wherein D1is the same as D2. ny-2932441Attorney Docket No.330272000440 25. The method of claim 23, wherein D1is different than D2.

26. A method of treating cancer, comprising administering a conjugate of claim 19 or claim 20.

27. The method of claim 26, further comprising administering a second drug (D2) in free (unconjugated) form.

28. The method of claim 27, wherein D1is the same as D2.

29. The method of claim 27, wherein D1is different than D2. ny-2932441

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