DRPSHP

Scientific Reference

Melanotan I (Afamelanotide)

Evidence profile: Human Phase 3 evidence

Melanotan I, or afamelanotide, is a synthetic 13-residue copy of alpha-melanocyte-stimulating hormone (alpha-MSH) with two deliberate edits. Norleucine stands in for methionine at position 4, and the phenylalanine at position 7 is the D-isomer. The natural hormone is a melanocortin, one of a family cut from the precursor pro-opiomelanocortin (POMC) that also includes ACTH and beta- and gamma-MSH. The analogue has been characterised in receptor-binding and cell assays and animal studies, and it has also been the subject of human clinical research. Melanotan II is a different compound: shorter and cyclic.

Mechanism of Action

There are five melanocortin receptors, MC1R to MC5R, all G-protein-coupled and signalling mainly via Gs, adenylyl cyclase and cyclic AMP. Afamelanotide is reported to bind MC1R with high affinity and to act at MC3R, MC4R and MC5R too, so it is not selective for one subtype. The two substitutions are placed with purpose: norleucine removes a methionine that oxidises easily, and the D-phenylalanine sits within the His-Phe-Arg-Trp sequence common to the natural melanocortins, where it is reported to raise receptor affinity and resistance to enzymatic breakdown. MC1R is found in skin and several immune cell types, MC4R mainly in the brain.

Molecular Information

  • Type: Melanocortin receptor agonist (alpha-MSH analog)
  • 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