Melanotan I is a linear tridecapeptide analogue of α-melanocyte-stimulating hormone (α-MSH), Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂, also designated [Nle4, D-Phe7]-α-MSH or NDP-α-MSH. It differs from native α-MSH by two non-natural substitutions: norleucine in place of methionine at position 4 and D-phenylalanine in place of L-phenylalanine at position 7. The analogue was described in 1980 as a potent, enzymatically stable melanotropin.

Melanotan I is reported to act as a high-affinity agonist at the melanocortin receptors MC1R, MC3R, MC4R and MC5R, with particularly high potency at MC1R. These class A GPCRs couple to Gs, and agonist binding increases adenylyl cyclase activity and intracellular cyclic AMP. Cryo-EM structures of MC1R–Gs and MC4R–Gs complexes bound to this peptide show the His-D-Phe-Arg-Trp core occupying the orthosteric pocket, with a bound calcium ion contributing to ligand recognition at MC1R.

Melanotan I is widely used as a reference agonist and, in radioiodinated form, as a radioligand in melanocortin receptor binding assays. Other research areas include GPCR structural biology, cAMP signalling studies in recombinant cell lines, and melanogenesis signalling and eumelanin synthesis pathways in melanocyte cultures.

Research use only. This material is sold for in-vitro laboratory research and development purposes exclusively. It is not a drug, food, or dietary supplement, has not been evaluated by the FDA, and must not be used in humans or animals.