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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.

Published: 2026-09-13Last updated: 2026-10-15Literature/identifier verification: 2026-09-13
Also known asMelanotan IMelanotan-1MT-IMT-1NDP-MSHNDP-alpha-MSHCUV1647MBJ05
Linear melanocortin analogs

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.

Canonical name: Afamelanotide.

Declared aliases and development codes: Melanotan I, Melanotan-1, MT-I, MT-1, NDP-MSH, NDP-alpha-MSH, CUV1647, MBJ05.

02

Molecular properties

Molecular formulaC78H111N21O19
Molecular mass1646.85 Da
CAS Registry Number75921-69-6
PubChem CID16197727
UNIIQW68W3J66U
Three-letter sequenceSer–Tyr–Ser–Nle–Glu–His–D-Phe–Arg–Trp–Gly–Lys–Pro–Val
Terminal groupsN-terminal acetylation; C-terminal amide

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.

03

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.

04

Molecular targets & mechanisms

Melanocortin receptors

MC1R · MC2R · MC3R · MC4R · MC5R · MCR

A family of five G protein-coupled receptors, MC1R through MC5R. ACTH recognition and signaling at MC2R depend on the accessory protein MRAP. Native hormones, peptide analogs and nonpeptide ligands differ in receptor-subtype recognition and functional direction; binding affinity, agonism and antagonism must be interpreted separately in the experimental system studied.

05

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.

Disagreements and mix-ups

Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.

What the studies reported

Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.

Cell and tissue studies

  • Frog skin bioassay

    Sawyer et al. reported prolonged biological activity of synthetic [Nle4, D-Phe7]-alpha-MSH in a frog skin bioassay.

    Reference [1]

  • Serum enzyme degradation assay

    Sawyer et al. found that [Nle4, D-Phe7]-alpha-MSH was resistant to enzymatic degradation by serum enzymes in vitro.

    Reference [1]

  • Human MC1R site-directed mutants

    Yang et al. reported that mutation of human MC1R residues Glu94, Asp117 or Asp121 significantly altered the binding affinity and potency of NDP-MSH in receptor assays.

    Reference [2]

  • MC4R-Gs receptor complex

    Zhang et al. reported a high-resolution structure of full-length MC4R in complex with heterotrimeric Gs protein and afamelanotide in vitro.

    Reference [4]

  • MC1R-Gs receptor complex

    Ma et al. reported a cryo-electron microscopy structure of an MC1R-Gs complex bound to afamelanotide in vitro.

    Reference [3]

  • Human MC4R-Gs receptor complex

    Heyder et al. reported a cryo-electron microscopy structure of human wild-type MC4R-Gs bound to NDP-alpha-MSH at 2.9 angstrom resolution in vitro.

    Reference [5]

  • Mouse melanoma cell biochemical assays

    Sawyer et al. reported activation of adenylate cyclase and stimulation of tyrosinase activity in mouse melanoma cell assays with [Nle4, D-Phe7]-alpha-MSH.

    Reference [1]

06

Verified bibliography

Cited studies by type

The 5 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.

A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.

  1. Reference 1

    4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.

    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

    current
    PMID 6777774PMC350149DOI 10.1073/pnas.77.10.5754Melanotan I (Afamelanotide)MC1R

  2. Reference 2

    Molecular basis for the interaction of [Nle4,D-Phe7]melanocyte stimulating hormone with the human melanocortin-1 receptor.

    Yang Yk, Dickinson C, Haskell-Luevano C, Gantz I

    The Journal of biological chemistry · 1997-09-12 · Journal Article

    current
    PMID 9287296DOI 10.1074/jbc.272.37.23000Melanotan I (Afamelanotide)MC1R

  3. Reference 3

    Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor.

    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

    current
    PMID 34453129PMC8486761DOI 10.1038/s41422-021-00557-yMelanotan I (Afamelanotide)alpha-MSHSHU9119MC1R

  4. Reference 4

    Structural insights into ligand recognition and activation of the melanocortin-4 receptor.

    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

    current
    PMID 34433901PMC8563965DOI 10.1038/s41422-021-00552-3PT-141 (Bremelanotide)Melanotan I (Afamelanotide)alpha-MSHTHIQSetmelanotideMC1R

  5. Reference 5

    Structures of active melanocortin-4 receptor-Gs-protein complexes with NDP-α-MSH and setmelanotide.

    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

    current
    PMID 34561620PMC8563958DOI 10.1038/s41422-021-00569-8PT-141 (Bremelanotide)Melanotan I (Afamelanotide)SetmelanotideMC1R

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Sawyer TK et al. 1980Study models reported: in vitro · from the full text
Yang Yk et al. 1997Study models reported: in vitro · from the abstract
Ma S et al. 2021Study models reported: in vitro · from the abstract
Zhang H et al. 2021Study models reported: in vitro · from the abstract
Heyder NA et al. 2021Study models reported: in vitro · from the abstract

Compare

Record history

Published 2026-09-13.

  • : Sequence and structure

Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.

Cite this record: Purely Peptides Research Library. Melanotan I (Afamelanotide). Published 2026-09-13; updated 2026-10-15. https://purelypeptides.org/research/compounds/melanotan-i/

10

Methodology & citation verification

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