Melanocortin Peptides

What Defines a Melanocortin Peptide?

The melanocortin system has three parts. There are five G protein-coupled melanocortin receptors. There are peptide agonists made from the proopiomelanocortin precursor. And there are two natural antagonists, agouti and agouti-related protein [R1]. The system has been linked to pigmentation, adrenal steroid production and energy balance in research models [R1].

A melanocortin peptide, in the sense used here, is a peptide based on α-MSH or a fragment of it. MC2R mainly recognizes ACTH. MC1R, MC3R, MC4R and MC5R all recognize α-MSH [R2]. Synthetic α-MSH analogues have long been used as tool compounds to probe these receptors [R6]. So this is a family defined by its parent hormone and its receptor targets, not by one shared motif.

The three compounds here sit at different points in that family. KPV is the last three residues of α-MSH [R3]. Melanotan I keeps all 13 residues but swaps two of them [R4][R8]. Melanotan II is a shorter, ring-closed version of the core sequence [R5].

Melanocortin Peptides Compared

Limits of the Evidence

Most KPV data come from cell lines and mouse colitis models [R3][R7]. Results in mice do not show what happens in other species. Receptor data for Melanotan II come largely from cloned receptors and isolated tissue assays [R2]. Potency in a receptor assay does not predict effects in a whole organism. Clinical trial data for afamelanotide apply to the approved, controlled product, not to research material [R12]. Batch identity and purity also vary between suppliers. Check each lot before use. Our guide on how to read a peptide COA explains what to look for.

Regulatory Status

Afamelanotide. FDA approved afamelanotide as a subcutaneous implant on October 8, 2019 (NDA 210797) [R11]. The approved indication is for adults with erythropoietic protoporphyria (EPP) who have a history of phototoxic reactions [R11]. Randomized controlled trials in EPP patients were published in 2015 [R12]. The Melanotan I sold here is a research peptide. It is not that approved drug product. It is not made, tested or labeled to drug standards.

Melanotan II. Melanotan II is not an FDA-approved drug. In a 2016 notice, FDA described a firm's Melanotan II product as "an unapproved new drug" sold online [R13]. FDA also lists Melanotan II among bulk substances with safety concerns. It cites published case reports of serious adverse events, including melanoma [R14]. Its nomination for the compounding bulks list was withdrawn [R14].

KPV. KPV is not an FDA-approved drug. FDA notes it has found no human exposure data for drug products containing KPV [R14]. FDA's Pharmacy Compounding Advisory Committee reviewed KPV on July 23, 2026 [R15]. FDA proposed that KPV not be added to the 503A bulks list [R16]. The committee voted 8 to 6, with one abstention, to recommend adding it [R17]. FDA makes the final decision. None of this changes the research-only status of the material sold here. Read more in RUO peptides explained.

FAQ

What do the peptides in this category have in common?

All three are based on α-MSH. KPV is a fragment of it. Melanotan I and Melanotan II are synthetic analogues [R3][R4][R5].

Is Melanotan I the same as the approved afamelanotide implant?

No. The molecule has the same sequence [R8][R9]. But the approved product is a finished drug made under FDA oversight [R11]. Our material is a research reagent only.

Does KPV act through melanocortin receptors?

Not fully. In mouse colitis models, KPV effects were seen partly independent of MC1R signaling [R3]. In cell studies it entered cells through the PepT1 transporter [R7].

Which receptors does Melanotan II bind?

Melanotan II has the structure Ac-Nle4-cyclo[Asp5,D-Phe7,Lys10]α-MSH(4–10)-NH2. A 1995 study called it a superpotent cyclic agonist and tested analogues at cloned MC1R, MC3R and MC4R [R2]. It is widely used as a reference ligand in receptor research [R6].

Are these products approved for human use?

No. They are sold for laboratory research only. They are not drugs, supplements or cosmetics.

References

1. Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27(7):736-749. doi:10.1210/er.2006-0034. PMID 17077189.
2. Hruby VJ, Lu D, Sharma SD, et al. Cyclic lactam α-melanotropin analogues of Ac-Nle4-cyclo[Asp5,D-Phe7,Lys10]α-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;38(18):3454-3461. doi:10.1021/jm00018a005. PMID 7658432.
3. Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. doi:10.1002/ibd.20334. PMID 18092346.
4. Sawyer TK, Sanfilippo PJ, Hruby VJ, et al. 4-Norleucine, 7-D-phenylalanine-α-melanocyte-stimulating hormone: a highly potent α-melanotropin with ultralong biological activity. Proc Natl Acad Sci U S A. 1980;77(10):5754-5758. doi:10.1073/pnas.77.10.5754. PMID 6777774.
5. U.S. Food and Drug Administration, Global Substance Registration System. Melanotan II, UNII UPF5CJ93X7. precision.fda.gov
6. Weirath NA, Haskell-Luevano C. Recommended tool compounds for the melanocortin receptor (MCR) G protein-coupled receptors (GPCRs). ACS Pharmacol Transl Sci. 2024;7(9):2706-2724. doi:10.1021/acsptsci.4c00129. PMID 39296259.
7. Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. doi:10.1053/j.gastro.2007.10.026. PMID 18061177.
8. U.S. Food and Drug Administration. Prescribing information, afamelanotide implant (NDA 210797), 2019. accessdata.fda.gov
9. U.S. Food and Drug Administration, Global Substance Registration System. Afamelanotide, UNII QW68W3J66U. precision.fda.gov
10. ChEBI (EMBL-EBI). Lys-Pro-Val, CHEBI:160254. ebi.ac.uk/chebi
11. U.S. Food and Drug Administration. NDA 210797 approval letter, afamelanotide implant. October 8, 2019. accessdata.fda.gov
12. Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015;373(1):48-59. doi:10.1056/NEJMoa1411481. PMID 26132941.
13. U.S. Food and Drug Administration. Notice of Opportunity for Hearing (NOOH): Manookian, Edward. August 5, 2016. fda.gov
14. U.S. Food and Drug Administration. Certain bulk drug substances nominated for use in compounding that may present significant safety risks. Content current as of April 22, 2026. fda.gov
15. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. fda.gov
16. U.S. Food and Drug Administration. FDA presentation: KPV (free base) and KPV acetate, Pharmacy Compounding Advisory Committee, July 23, 2026. fda.gov
17. McDermott Will & Schulte. Bulk list bound? PCAC backs majority of peptides in two-day public meeting. July 27, 2026. mcdermottlaw.com

For laboratory research use only. Not for human or veterinary use.