Cobalt PeptidesResearch Grade

Scientific Reference

Melanotan I (Afamelanotide)

Evidence profile: Human Phase 3 evidence

Melanotan I, also known as afamelanotide, is a 13-residue synthetic analogue of alpha-melanocyte-stimulating hormone (α-MSH). It differs from the natural hormone at two positions: norleucine takes the place of methionine at position 4, and the phenylalanine at position 7 is the D-isomer. The parent hormone is one of the melanocortins, a family of peptides cut from the precursor pro-opiomelanocortin (POMC) that also includes adrenocorticotropic hormone (ACTH) and β- and γ-MSH. The analogue has been characterised in receptor-binding and cell assays and in animal studies, and it has also been the subject of human clinical research. Melanotan II is a separate, shorter and cyclic analogue.

Mechanism of Action

The melanocortin receptors are five G-protein-coupled receptors, MC1R to MC5R, that signal mainly through Gs, adenylyl cyclase and cyclic AMP. Afamelanotide has been reported to bind MC1R with high affinity and to act at MC3R, MC4R and MC5R as well, so it is not selective for a single subtype. Its two substitutions sit at deliberate points: norleucine removes a methionine that oxidises readily, and the D-phenylalanine lies within the His-Phe-Arg-Trp sequence shared by the natural melanocortin peptides, where it has been reported to raise receptor affinity and resistance to enzymatic breakdown. MC1R is expressed in skin and on several immune-cell types, and MC4R mainly in the brain.

Molecular Information

  • Type: Melanocortin receptor agonist (α-MSH analog)
  • Length: 13 amino acids
  • Molecular weight: 1646.8 g/mol
  • Molecular formula: C78H111N21O19
  • CAS: 75921-69-6

Published Research

  • Afamelanotide for Erythropoietic Protoporphyria

    Langendonk JG et al. · The New England journal of medicine · 2015 · Clinical

    PMID 26132941 — View on PubMed

  • Evaluation of the immunogenicity of the synthetic α-melanocyte-stimulating hormone (α-MSH) analogue afamelanotide ([Nle4-D-Phe7]-α-MSH, Scenesse®) in erythropoietic protoporphyria patients by ELISA detecting both anti-afamelanotide and anti-α-MSH antibodies

    Lengweiler S et al. · Skin pharmacology and physiology · 2015 · Clinical

    PMID 25402764 — View on PubMed

  • Beneficial effects of the melanocortin analogue Nle4-D-Phe7-α-MSH in acne vulgaris

    Böhm M et al. · Journal of the European Academy of Dermatology and Venereology : JEADV · 2014 · Clinical

    PMID 22845050 — View on PubMed

  • Efficacy of the melanocortin analogue Nle4-D-Phe7-α-melanocyte-stimulating hormone in the treatment of patients with Hailey-Hailey disease

    Biolcati G et al. · Clinical and experimental dermatology · 2014 · Clinical

    PMID 24256215 — View on PubMed

  • [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers

    Barnetson RS et al. · The Journal of investigative dermatology · 2006 · Clinical

    PMID 16763547 — View on PubMed