Melanotan I (MT-1)

Melanotan I — afamelanotide in the clinical literature — is a linear tridecapeptide analogue of alpha-melanocyte stimulating hormone. Two substitutions against the native sequence, Nle⁴ and D-Phe⁷, slow enzymatic degradation and extend its usable half-life considerably.

Unlike its successor it remains linear rather than cyclic, and it is substantially selective for the melanocortin-1 receptor. That receptor sits on melanocytes and controls the switch between the two forms of melanin, which is the pathway the compound is used to interrogate.

MC1R signalling is the organising subject. Work using MT-1 covers:

• Melanogenesis — the synthesis of eumelanin and its regulation at receptor level

• Photoprotection research, where melanin density is the measured variable

• Erythropoietic protoporphyria, the indication afamelanotide was developed and approved for in clinical medicine

• Receptor subtype selectivity, using MT-1 as the MC1R-selective reference against broader melanocortin ligands

The melanocortin family has five receptor subtypes with very different roles — pigmentation, steroidogenesis, energy balance, sexual function, exocrine regulation. A ligand acting at one of them lets an experiment attribute an observation to that subtype. MT-1 is used where MC1R is the question, and MT-2 where it is not.

Melanotan II is the cyclic, non-selective counterpart, and PT-141 is a metabolite of MT-2 studied at MC3R and MC4R rather than MC1R. The three together are the standard set for separating melanocortin subtype effects.