MT1

Overview

Melanotan I (MT1), also known as afamelanotide, is a synthetic linear tridecapeptide analog of α-melanocyte-stimulating hormone (α-MSH). It has a [Nle4, D-Phe7] substitution that dramatically increases its potency and metabolic stability compared to native α-MSH. MT1 is more selective for the MC1R receptor than Melanotan II, making it a preferred research tool for studying melanogenesis without significant off-target melanocortin receptor effects. Under the brand name Scenesse, afamelanotide received EMA and FDA approval for erythropoietic protoporphyria (EPP).

Mechanism of Action

MT1 binds with high affinity and selectivity to MC1R on epidermal melanocytes. MC1R activation triggers the Gs-adenylate cyclase-cAMP-PKA cascade, leading to phosphorylation of CREB and upregulation of MITF (microphthalmia-associated transcription factor). MITF then transcriptionally activates the melanogenic enzymes tyrosinase, TRP-1, and TRP-2, driving the conversion of L-tyrosine through L-DOPA to eumelanin. The shift toward eumelanin (brown-black pigment) over pheomelanin (red-yellow, pro-oxidant) provides the photoprotective basis studied in UV-damage research.

Research Applications

• MC1R-selective melanogenesis research
• Eumelanin vs pheomelanin switching studies
• UV photoprotection and DNA damage prevention models
• Melanocyte biology and MITF transcription research
• Comparative melanocortin receptor selectivity studies