DRPSHP

Scientific Reference

Melanotan II

Evidence profile: Human Phase 1 evidence

Melanotan II is a cyclic seven-residue analogue of alpha-melanocyte-stimulating hormone (alpha-MSH), held in its ring by a lactam bridge: an amide bond between the side chains of aspartic acid and lysine. Inside that ring sits His-D-Phe-Arg-Trp, the receptor-binding core shared by the melanocortin peptides. An acetylated norleucine lies outside the ring and the C-terminus is amidated, which makes the molecule much shorter and more constrained than the 13-residue parent hormone. In rodent research it is a standard reference melanocortin agonist; human data are confined to a few small early studies. Bremelanotide (PT-141) differs from it only at the C-terminus.

Mechanism of Action

Melanotan II is reported to be an agonist at MC1R, MC3R, MC4R and MC5R and is regarded as non-selective among them. All are G-protein-coupled receptors that signal chiefly through Gs and cyclic AMP. MC3R and MC4R are expressed in the hypothalamus and other brain areas, which is why the peptide has been used so widely in rodent studies of central melanocortin signalling; at those receptors it acts in opposition to agouti-related peptide, an endogenous antagonist and inverse agonist. The lactam ring is thought to hold the core residues in a turn that favours receptor binding.

Molecular Information

  • Type: Cyclic heptapeptide (alpha-MSH analog)
  • Molecular weight: 1024.2 g/mol
  • Molecular formula: C50H69N15O9
  • CAS: 121062-08-6

Published Research

  • Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review

    Habbema L et al. · International journal of dermatology · 2017 · Review

    PMID 28266027 — View on PubMed

  • Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study

    Dorr RT et al. · Life sciences · 1996 · Clinical

    PMID 8637402 — View on PubMed

  • Melanotan II: a possible cause of renal infarction: review of the literature and case report

    Peters B et al. · CEN case reports · 2020 · Review

    PMID 31953620 — View on PubMed

  • Melanotan-associated melanoma

    Paurobally D et al. · The British journal of dermatology · 2011 · Preclinical

    PMID 21564053 — View on PubMed