Compound monograph
Melanotan I (Afamelanotide)
Afamelanotide, widely supplied as Melanotan I, is a linear thirteen-residue analog of alpha-melanocyte-stimulating hormone carrying norleucine and D-phenylalanine substitutions.
01
Identity & nomenclature
Afamelanotide, widely supplied as Melanotan I, is a linear thirteen-residue analog of alpha-melanocyte-stimulating hormone carrying norleucine and D-phenylalanine substitutions.
Melanotan I and afamelanotide are the same defined peptide. One name is commercial, the other the standardised substance name; they are not two different sequences. The opposite error is equally wrong: shared peptide identity does not make a research vial equivalent to a finished pharmaceutical product, and a product brand name is not an additional peptide. Most importantly, Melanotan I is NOT Melanotan II — this is a linear thirteen-residue analog, that is a cyclic lactam heptapeptide, and they differ in formula and mass. The unqualified word 'melanotan' is not a usable identity field.
Declared aliases and development codes: Melanotan I, Melanotan-1, MT-I, MT-1, NDP-MSH, NDP-alpha-MSH, CUV1647, MBJ05.
02
Molecular properties
| Molecular formula | C78H111N21O19 |
|---|---|
| Molecular mass | 1646.85 Da |
| CAS Registry Number | 75921-69-6 |
| PubChem CID | 16197727 |
| UNII | QW68W3J66U |
| Three-letter sequence | Ac–Ser–Tyr–Ser–Nle–Glu–His–D-Phe–Arg–Trp–Gly–Lys–Pro–Val–NH2 |
Thirteen residues, LINEAR — no disulfide and no lactam bridge. Nle is L-norleucine, substituted for the methionine of alpha-MSH; position 7 is D-phenylalanine. N-terminally acetylated and C-terminally amidated.
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Structural characteristics
An afamelanotide-bound MC1R–Gs complex has been determined, making this an exact-compound receptor structure rather than an analog structure. The compound is not MC1R-exclusive: it also stimulates MC3, MC4 and MC5 receptors in receptor assays, and a receptor-bound NDP-alpha-MSH–MC4R structure demonstrates activity at MC4R directly. A product description reading 'MC1R agonist' must not be restated as absence of activity at the other subtypes. An assay-independent quantitative selectivity ranking across the subtypes is not established.
- Met4 to L-norleucine substitution
- L-Phe7 to D-Phe substitution
Terminal features: N-terminal acetylation, C-terminal amide.
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Molecular targets & mechanisms
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Analytical considerations
Two features are invisible to routine intact mass. D-phenylalanine and L-phenylalanine have identical elemental composition, and norleucine is a constitutional isomer of leucine and isoleucine — also identical. Ordinary peptide fragment masses do not establish D/L configuration either. Confirming this compound requires hydrolysis followed by chiral amino-acid analysis with racemization controls and authentic standards, plus a method that distinguishes norleucine from leucine and isoleucine. N-acetylation and C-terminal amidation need separate confirmation. For acetate material, acetate stoichiometry is not derivable from the peptide ion and must be measured, as must water content; a peptide mass match does not convert chromatographic area purity into peptide content.
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Verified bibliography
- 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.current
Sawyer TK, Sanfilippo PJ, Hruby VJ, Engel MH, Heward CB, Burnett JB, Hadley ME
Proceedings of the National Academy of Sciences of the United States of America · 1980-10 · Journal Article
- Molecular basis for the interaction of [Nle4,D-Phe7]melanocyte stimulating hormone with the human melanocortin-1 receptor.current
Yang Yk, Dickinson C, Haskell-Luevano C, Gantz I
The Journal of biological chemistry · 1997-09-12 · Journal Article
- Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor.current
Ma S, Chen Y, Dai A, Yin W, Guo J, Yang D, Zhou F, Jiang Y, Wang MW, Xu HE
Cell research · 2021-08-27 · Journal Article
- Structural insights into ligand recognition and activation of the melanocortin-4 receptor.current
Zhang H, Chen LN, Yang D, Mao C, Shen Q, Feng W, Shen DD, Dai A, Xie S, Zhou Y, Qin J, Sun JP, Scharf DH, Hou T, Zhou T, Wang MW, Zhang Y
Cell research · 2021-08-25 · Journal Article
- Structures of active melanocortin-4 receptor-Gs-protein complexes with NDP-α-MSH and setmelanotide.current
Heyder NA, Kleinau G, Speck D, Schmidt A, Zschunke S, Szczepek M, Bauer B, Koch A, Gallandi M, Kwiatkowski D, Bürger J, Mielke T, Beck-Sickinger AG, Hildebrand PW, Spahn CMT, Hilger D, Schacherl M, Biebermann H, Hilal T, Kühnen P, Kobilka BK, Scheerer P
Cell research · 2021-09-24 · Journal Article
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Methodology & citation verification
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