Melanotan II

Melanotan-II is a non-selective melanocortin receptor agonist with activity at MC1R, MC3R, and MC4R — receptor binding and signaling characterization^[1]

This in vitro pharmacological study characterized Melanotan-II's receptor binding affinity and functional potency at all five melanocortin receptor subtypes (MC1R-MC5R) using radioligand competition assays and cAMP accumulation in heterologous expression systems. Melanotan-II demonstrated high affinity at MC1R (Ki ~0.2 nM), MC3R (Ki ~0.3 nM), and MC4R (Ki ~0.6 nM), with substantially lower affinity at MC2R and MC5R. Functional cAMP assays confirmed that Melanotan-II acts as a full agonist at MC1R and MC4R and a partial agonist at MC3R. The non-selectivity profile and cyclic structure were noted as distinguishing features relative to the linear parent peptide alpha-MSH, and the data supported Melanotan-II's use as a tool compound for melanocortin receptor biology research.

Last verified: 2026-04-03

MC1R-mediated melanogenesis and the role of Melanotan-II in preclinical pigmentation research^[2]

This study evaluated the melanogenic activity of Melanotan-II in B16-F10 melanoma cells and primary human melanocytes to characterize MC1R-dependent melanin synthesis. Melanotan-II at 1-100 nM significantly increased intracellular melanin content as measured by spectrophotometric absorbance, with an EC50 approximately 10-fold lower than alpha-MSH. Upstream signaling analysis confirmed cAMP accumulation and PKA-dependent phosphorylation of CREB, which transactivated the MITF promoter and subsequently upregulated tyrosinase, the rate-limiting enzyme in melanin biosynthesis. The authors used Melanotan-II as a pharmacological tool to dissect MC1R pathway stoichiometry in melanocyte biology, noting its utility as a potent and stable MC1R agonist for in vitro pigmentation research.

Last verified: 2026-04-03