Melanotan I (Afamelanotide, CUV1647) is a linear synthetic ฮฑ-MSH analogue with [Nleโด, D-Pheโท] substitutions that enhance MC1R binding affinity and metabolic stability. Unlike the cyclic Melanotan II, MT-1 is highly selective for MC1R, making it the preferred research tool for isolated melanocortin-1 receptor studies. It is FDA-approved (as Scenesseยฎ) for prevention of phototoxicity in erythropoietic protoporphyria.
CAS 75921-69-6 | MW 1646.9 DaHigh selectivity for melanocortin-1 receptor vs MT-II which activates MC3R/MC4R broadly. Key for receptor-specific research.
Activates eumelanin synthesis pathway via MC1R-cAMP-PKA-MITF cascade. Produces photoprotective dark melanin.
Clinical data demonstrates MT-1 implants reduce phototoxic reactions in EPP patients โ the basis of FDA approval.
MC1R activation has anti-inflammatory effects in skin โ distinct from MC3R-mediated pathways activated by MT-II.
Langendonk et al. demonstrated afamelanotide implants significantly reduced phototoxic reactions and improved quality of life in EPP patients โ leading to FDA approval in 2019.
N Engl J Med. 2015;373(1):48โ59Bednarek et al. established Melanotan I as the most MC1R-selective non-peptide-comparable reference, contrasting its linear structure with cyclic MT-II across all five MC receptor subtypes.
Biochemistry. 1999;38(47):15522โ15527MT-1 increased melanin index and reduced UV-induced DNA damage in Fitzpatrick skin type I-II subjects, supporting photoprotection research applications.
J Invest Dermatol. 2006;126(7):1536โ1542EPP clinical dose: 16mg biodegradable implant (Scenesse). Research SC protocols use 0.16โ1.6 mg doses. In vitro MC1R studies: 1โ100 nM. Melanin quantification (absorbance/imaging), MC1R binding assay, and cAMP production are standard endpoints. Compare directly to MT-II for receptor subtype differentiation studies.
| Full Name | Melanotan I (Afamelanotide) |
| CAS Number | 75921-69-6 |
| Molecular Weight | 1646.9 Da |
| Selectivity | MC1R preferred |
| FDA Status | Approved (Scenesse) for EPP |
| Purity | โฅ99% by HPLC |
| Appearance | White lyophilized powder |
| Storage | โ20ยฐC, desiccated |
