Melanotan II is a synthetic cyclic heptapeptide analogue of α-MSH, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂. It corresponds to a truncated α-MSH(4–10) core in which a lactam bridge between the side chains of Asp5 and Lys10 closes a 23-membered ring. Its non-natural features are an N-terminal acetyl-norleucine, a D-phenylalanine and a C-terminal amide. The compound arose from conformation-based design of cyclic lactam melanotropins published in 1989.

Melanotan II is reported to be a potent, largely non-selective agonist at the melanocortin receptors MC1R, MC3R, MC4R and MC5R, but not MC2R, which is selective for ACTH. Through these Gs-coupled class A GPCRs it increases adenylyl cyclase activity and cyclic AMP. Replacing D-Phe7 with the bulkier D-2′-naphthylalanine converts the same scaffold into the MC3R/MC4R antagonist SHU9119, and the pair is a classic tool set in melanocortin pharmacology.

Research using Melanotan II spans melanocortin receptor binding and cAMP assays in recombinant cell lines, structure–activity studies of cyclic lactam peptides, hypothalamic neuropeptide signalling in rodent tissue and cell models, and melanogenesis signalling in melanocyte cultures. It is frequently paired with antagonists such as SHU9119 to assign receptor subtypes.

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.