What are melanocortin peptides?
Melanocortins are peptides cut from one precursor protein, proopiomelanocortin (POMC). They include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH), and they act at five G protein-coupled receptors, MC1R to MC5R (Dores et al., 2014). In research, the term also covers synthetic analogs, several designed to be superpotent, prolonged-acting and enzyme-resistant (Hadley and Dorr, 2006), and fragments such as KPV, the C-terminal tripeptide of alpha-MSH. Disguised Alpha supplies Melanotan 2, PT-141 and KPV as 10 mg lyophilized powders for laboratory research use only. Nothing on this page is guidance for use in people.
The melanocortin system
Alpha-MSH, one of the peptides cut from POMC, has 13 residues (PubChem CID 16133793). Melanocortin system research maps each receptor to a role and site:
- MC1R: pigmentation (Dores et al., 2014). The Vyleesi label notes that it is expressed on melanocytes.
- MC2R: glucocorticoid synthesis, within the hypothalamus-pituitary-adrenal axis. It responds only to ACTH (Dores et al., 2014).
- MC3R and MC4R: expressed primarily in the central nervous system (Molinoff et al., 2003) and tied to energy homeostasis (Dores et al., 2014).
- MC5R: found in a number of peripheral tissues (Hruby et al., 1995), with a role in exocrine gland physiology (Dores et al., 2014).
The system also makes its own antagonists. Agouti protein is normally limited to the skin, where it affects pigmentation. Agouti-related protein (AgRP) is expressed in the hypothalamus, and in vitro, recombinant AgRP was a potent, selective antagonist of MC3R and MC4R (Ollmann et al., 1997). A later review describes the AgRPs as reverse agonists (Dores et al., 2014).
From alpha-MSH to melanotan, PT-141 and KPV
Swapping methionine 4 for norleucine and phenylalanine 7 for D-phenylalanine gave [Nle4, D-Phe7]-alpha-MSH, also called NDP-MSH. In the 1980 report, it resisted serum enzymes, acted longer in a frog skin bioassay and was 26 times as potent as alpha-MSH in a mouse melanoma adenylate cyclase assay (Sawyer et al., 1980). Two analogs were later patented and tested clinically: melanotan I, a linear peptide, and melanotan II, a cyclic truncated peptide. PT-141 followed as a melanotan II analog (Hadley and Dorr, 2006).
- Melanotan I is NDP-MSH itself: PubChem lists melanotan I, NDP-MSH and afamelanotide, its nonproprietary name, as one 13-residue peptide (CID 16197727). It appears here as research history only.
- Melanotan II (melanotan 2), Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, is built on alpha-MSH residues 4 to 10, with a lactam bridge between Asp and Lys closing the ring (PubChem CID 92432).
- PT-141 (bremelanotide) keeps that ring but ends in a free carboxylic acid instead of an amide (PubChem CID 9941379).
- KPV, Lys-Pro-Val, is alpha-MSH residues 11 to 13 (PubChem CID 125672). It lacks His-Phe-Arg-Trp, the core melanocortin sequence, and research on it centers on inflammation models (Getting et al., 2003).
Our three catalog peptides ship as lyophilized powder; their product pages list -20°C storage, protected from light, and 2 to 8°C after reconstitution. See what lyophilized means.
Melanocortin peptides at a glance
Profiles come from the sources cited on this page.
| Peptide | Origin | Receptor profile | Regulatory status | Our guide |
|---|---|---|---|---|
| Alpha-MSH | Natural; 13 residues cut from POMC | Recognized by MC1R, MC3R, MC4R and MC5R; MC2R responds only to ACTH | Endogenous hormone | None |
| AgRP | Natural; expressed in the hypothalamus | Selective antagonist (reverse agonist) at MC3R and MC4R | Endogenous protein | None |
| Afamelanotide (NDP-MSH, melanotan I) | Synthetic linear alpha-MSH analog, reported 1980 | Recognized by MC1R, MC3R, MC4R and MC5R; label says it binds predominantly to MC1R | FDA approved in 2019 as the implant Scenesse, for one rare light-sensitivity disorder | Melanotan 1 in the catalog; no cited guide yet |
| Melanotan II | Synthetic cyclic lactam analog of alpha-MSH(4-10) | Non-selective agonist at MC1R, MC3R, MC4R and MC5R | Not an approved drug; FDA cites immunogenicity risk and case reports | Melanotan II guide |
| PT-141 (bremelanotide) | Melanotan II analog with a free C-terminal acid | Non-selective agonist; label potency order MC1R, MC4R, MC3R, MC5R, MC2R | FDA approved in 2019 as Vyleesi, for one indication in premenopausal women | PT-141 guide |
| KPV | C-terminal tripeptide of alpha-MSH (residues 11 to 13) | In mice, acted without functional MC1R and with MC3/4 receptors blocked; enters intestinal cell lines through PepT1 | Not an approved drug; FDA has identified no human exposure data | KPV guide |
Receptor selectivity of melanocortin receptor agonists
MC4R shares high sequence similarity with the other receptors, and low agonist selectivity has hampered the design of MC4R-selective agents (Zhang et al., 2021).
Melanotan II and SHU9119
A 1995 paper notes that MC1R, MC3R, MC4R and MC5R all recognize alpha-MSH, NDP-MSH and melanotan II, while MC2R primarily recognizes only ACTH. In its tests, putting the bulkier D-2'-naphthylalanine in place of D-Phe7 in melanotan II changed the profile. The new analog was a potent antagonist at MC4R, a weaker antagonist at MC3R and a full agonist at MC1R and MC5R (Hruby et al., 1995).
That analog, SHU9119, blunted the cAMP rise melanotan II caused in macrophages in a later mouse inflammation study (Getting et al., 2003). A 2020 review calls melanotan II a non-selective melanocortin receptor agonist (Peters et al., 2020).
PT-141 and afamelanotide
PT-141 is an agonist at melanocortin receptors including MC3R and MC4R (Molinoff et al., 2003). The FDA label of its drug product says it activates several subtypes nonselectively, in this order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. The afamelanotide label says it binds predominantly to MC1R. Even so, structures of MC4R with its G protein, bound to alpha-MSH, afamelanotide or bremelanotide, show a conserved binding mode for these peptide agonists (Zhang et al., 2021).
KPV: outside the classical receptors
In a mouse model of crystal-induced peritonitis, KPV reduced polymorphonuclear leukocyte accumulation, and SHU9119 did not block the effect. Unlike melanotan II, KPV did not raise cAMP in macrophages, and it still acted in mice with a non-functional MC1R. The authors concluded that KPV more likely acts by inhibiting IL-1beta functions than through melanocortin receptors (Getting et al., 2003).
In human intestinal epithelial and T cell lines, nanomolar KPV inhibited NF-kappaB and MAP kinase signaling and entered cells through the peptide transporter PepT1. Added to drinking water, it lowered pro-inflammatory cytokine expression in two chemically induced mouse colitis models (Dalmasso et al., 2008).
Links to oxytocin and kisspeptin research
Melanocortin signaling reaches other hypothalamic peptide systems. In rats, central alpha-MSH and selective MC4R agonists inhibited the electrical activity of supraoptic oxytocin neurons, and central alpha-MSH lowered oxytocin secretion into the blood. Yet MC4R ligands triggered substantial oxytocin release from dendrites in isolated supraoptic nuclei (Sabatier et al., 2003). In pubertal rats, central alpha-MSH signaling activated the reproductive axis. In rodent models, gonadotropic responses to MC3/4R activation were markedly attenuated when kisspeptin receptors were absent or arcuate Kiss1 neurons were inhibited (Manfredi-Lozano et al., 2016). See our oxytocin acetate guide and kisspeptin guide.
Regulatory status and safety reports
Of the synthetic peptides on this page, two are FDA-approved drugs, each for one indication. Afamelanotide, as the implant Scenesse, was FDA approved in October 2019 to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria; the EU had authorised it in 2014.
Bremelanotide, as Vyleesi, was FDA approved in June 2019 for premenopausal women with acquired, generalized hypoactive sexual desire disorder. The research-grade PT-141 sold here is not that drug product. Drugs@FDA lists no melanotan II or KPV product, and lists melanotan I only as afamelanotide, the Scenesse implant (openFDA search, October 2026).
An FDA page on bulk drug substances that may present significant safety risks lists Melanotan II and KPV among substances once in category 2 of its compounding interim policies whose nominations were withdrawn. It says compounded Melanotan II may pose a risk of immunogenicity for certain routes and cites published case reports of serious adverse events, including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism. For KPV, it notes no identified human exposure data. FDA Import Alert 66-41, on unapproved new drugs promoted in the United States, lists melanotan I and II products from three firms.
A 2017 dermatology review of unregulated melanotan use summarized case reports of changes in existing moles, newly emerging dysplastic nevi and four melanomas arising during or shortly after use, noted that conclusive evidence of a causal link is lacking, and reported that multiple national health organizations have issued safety warnings (Habbema et al., 2017).
Case reports describe a melanoma that coincided with melanotan II use (Hjuler and Lorentzen, 2014) and a renal infarction the authors attributed most likely to it (Peters et al., 2020). The afamelanotide label also warns that it may darken pre-existing nevi. The PT-141 guide covers the bremelanotide trial safety data.
Key sources
- Hruby VJ, et al. "Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors." J Med Chem. 1995. PMID 7658432. DOI 10.1021/jm00018a005.
- Hadley ME, Dorr RT. "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization." Peptides. 2006. PMID 16412534. DOI 10.1016/j.peptides.2005.01.029.
- Getting SJ, et al. "Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides." J Pharmacol Exp Ther. 2003. PMID 12750433. DOI 10.1124/jpet.103.051623.
- Zhang H, et al. "Structural insights into ligand recognition and activation of the melanocortin-4 receptor." Cell Res. 2021. PMID 34433901. DOI 10.1038/s41422-021-00552-3.
Frequently asked questions
What are melanocortin peptides?
Peptides cut from POMC, such as alpha-MSH and ACTH, that act at the five melanocortin receptors (Dores et al., 2014). The term also covers synthetic analogs such as afamelanotide, melanotan II and PT-141 (Hadley and Dorr, 2006).
What are melanocortin receptor agonists?
Compounds that activate one or more of MC1R to MC5R. Alpha-MSH, NDP-MSH and melanotan II are recognized by MC1R, MC3R, MC4R and MC5R; MC2R primarily recognizes only ACTH (Hruby et al., 1995).
What are MC4R agonist peptides?
Peptides that activate MC4R, a receptor expressed mainly in the brain. Alpha-MSH, afamelanotide, melanotan II and PT-141 all do, but none is selective. PT-141's label lists MC1R as its most potent target, and MC4R structures bound to alpha-MSH, afamelanotide or bremelanotide show one conserved binding mode (Zhang et al., 2021).
What are alpha-MSH analogs?
Synthetic peptides modeled on alpha-MSH, such as linear NDP-MSH (Sawyer et al., 1980) and the cyclic, truncated melanotan II and PT-141 (Hadley and Dorr, 2006).
Is melanotan 1 the same as afamelanotide?
Yes. PubChem lists melanotan I, NDP-MSH and afamelanotide as one peptide (CID 16197727). As the implant Scenesse, afamelanotide is an FDA-approved drug for one indication.
Where can researchers buy melanocortin peptides?
Disguised Alpha lists Melanotan 1, Melanotan 2, PT-141 and KPV as 10 mg lyophilized powders for laboratory research, with lot certificates on each product page and in the COA portal.
Related guides
- Melanotan II research guide
- PT-141 research guide
- KPV research guide
- Oxytocin acetate research guide
- Kisspeptin research guide
- What is a peptide?
- What does lyophilized mean?
- What is a COA?
- COA portal: published certificates, by lot
- Research hub
Disguised Alpha products are for research use only. They have not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.