Melanotan 1 (MT-1, Afamelanotide, also designated [Nle4, D-Phe7]-α-MSH or NDP-MSH) is a synthetic linear tridecapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH). The native α-MSH sequence was modified at two positions: methionine at position 4 was replaced with norleucine (Nle4) to prevent oxidative degradation, and L-phenylalanine at position 7 was substituted with D-phenylalanine (D-Phe7) to enhance receptor binding affinity and metabolic stability. These modifications produce a superpotent melanocortin agonist with approximately 100-fold greater potency than native α-MSH at the MC1R receptor.
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MT-1 signals primarily through the melanocortin 1 receptor (MC1R), a Gs-coupled GPCR expressed on melanocytes in the basal layer of the epidermis. MC1R activation stimulates adenylyl cyclase → cAMP → PKA → CREB signaling, which upregulates microphthalmia-associated transcription factor (MITF) expression. MITF drives transcription of melanogenic enzymes including tyrosinase (the rate-limiting enzyme converting L-tyrosine to L-DOPA and then to dopaquinone), TRP-1 (tyrosinase-related protein 1), and TRP-2 (dopachrome tautomerase), resulting in increased eumelanin synthesis and melanosome transfer to surrounding keratinocytes. This MC1R-selective profile distinguishes MT-1 from Melanotan 2, which has broader melanocortin receptor activity across MC1R, MC3R, MC4R, and MC5R.
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Research applications center on melanocyte biology and photoprotection mechanisms. Published studies have demonstrated that MT-1 increases melanin density in skin biopsies, enhances the ratio of photoprotective eumelanin to phototoxic pheomelanin, and may provide protection against UV-induced DNA damage (cyclobutane pyrimidine dimers and 6-4 photoproducts) in skin models. MC1R signaling is also linked to DNA repair mechanisms independent of melanin production — MC1R activation enhances nucleotide excision repair (NER) capacity through PKA-mediated phosphorylation of ATR and XPC.
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Supplied as a lyophilized powder with ≥99% purity. Store at -20°C desiccated. For melanocyte biology and photobiology research only.
