The parent: α-MSH
α-Melanocyte-stimulating hormone is a 13-residue peptide cut from the larger pro-opiomelanocortin protein, the same precursor that yields ACTH and β-endorphin. It acts on a family of five melanocortin receptors. MC1R on melanocytes controls pigmentation; MC3R and MC4R in the brain are involved in energy balance and sexual function; MC5R sits in exocrine glands; MC2R is the ACTH receptor. Which receptors an analogue reaches, and how selectively, decides what it does.
Two fragments, two purposes
| Compound | Structure | Receptor profile | Origin | Cited studies | Status |
|---|---|---|---|---|---|
| Melanotan II | Cyclic lactam heptapeptide, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2. The core His-Phe-Arg-Trp motif of α-MSH, cyclised and with a D-phenylalanine for stability. | Non-selective agonist across MC1R, MC3R, MC4R and MC5R | University of Arizona, Hruby and Hadley groups, 1980s–1990s | Hadley and Dorr (2006) review the development history. Wessells and colleagues (1998) ran a double-blind placebo-controlled crossover in men with psychogenic erectile dysfunction; the peptide initiated erections in most subjects, with nausea and flushing as side effects. | Never approved. Regulators in the United States, United Kingdom and Australia have issued warnings about unregulated "tanning" products containing it. |
| KPV | Linear tripeptide Lys-Pro-Val, residues 11–13 of α-MSH | Anti-inflammatory activity that does not depend on the pigmentation receptor | Identified as the minimal anti-inflammatory fragment of α-MSH | Dalmasso and colleagues (2008) showed uptake by the PepT1 transporter in intestinal cells and reduced inflammation in two mouse colitis models. Brzoska and colleagues (2008) review the mechanism. | Preclinical only. |
The relatives that did reach approval
Melanotan II is the parent of a small family, and two of its relatives are approved medicines. That is worth knowing because it shows what the scaffold can do when a single receptor is targeted, and because the names get confused.
- Afamelanotide, also known as Melanotan I, is a linear 13-residue analogue of α-MSH selective for MC1R. It is approved as an implant for erythropoietic protoporphyria, a light-sensitivity disorder, in the European Union since 2014 and the United States since 2019.
- Bremelanotide, formerly PT-141, is the C-terminal carboxylic-acid metabolite of Melanotan II: the same cyclic sequence with the terminal amide replaced by a free acid. It was developed from the erectile-function observation in the Wessells study and approved in the United States in 2019 for hypoactive sexual desire disorder in premenopausal women.
- Setmelanotide is a cyclic MC4R-selective agonist approved in 2020 for obesity caused by specific genetic deficiencies in the melanocortin pathway.
Melanotan II itself, the non-selective parent, was never developed to approval. Its breadth across receptors is what made it a research tool and what made it unsuitable as a medicine.
Why KPV is on the "repair" shelf
The C-terminal tripeptide keeps the anti-inflammatory activity of α-MSH and loses the pigmentation activity, because pigmentation needs the central His-Phe-Arg-Trp motif that KPV does not contain. The two compounds on this page are therefore complementary pieces of the same hormone: Melanotan II is the receptor-active core, KPV is the tail. KPV is compared with the other repair-shelf compounds on the repair peptide comparison.
Handling notes
- Melanotan II contains tryptophan, which is light-sensitive; keep solutions in the dark. The cyclic lactam and D-phenylalanine make it more resistant to enzymatic breakdown than the linear parent, but not to oxidation.
- KPV has no oxidation-prone residues. Standard cold, dark storage applies.
- Storage horizons by form are on the storage guide.
In our catalog
Melanotan II and KPV, each with specifications, the references above with PubMed links, and the certificate for the lot in stock where one exists.