Cobalt PeptidesResearch Grade

Scientific Reference

Melanotan II (MT-II)

Evidence profile: Human Phase 1 evidence

Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (α-MSH), closed by a lactam bridge. The ring is formed by an amide bond between the side chains of aspartic acid and lysine, and it encloses His-D-Phe-Arg-Trp, the receptor-binding core of the melanocortin peptides. With an acetylated norleucine outside the ring and an amidated C-terminus, it is much shorter and more conformationally constrained than the 13-residue parent hormone. It is widely used in rodent research as a reference melanocortin agonist, and human data are limited to a few small early studies. Bremelanotide (PT-141) differs from it only at the C-terminus.

Mechanism of Action

Melanotan II has been reported to act as an agonist at MC1R, MC3R, MC4R and MC5R, and it is regarded as non-selective among them. Each is a G-protein-coupled receptor that signals mainly through Gs and cyclic AMP. MC3R and MC4R are expressed in the hypothalamus and other brain regions, which is why the peptide has been used so often in rodent work on central melanocortin signalling. At those two receptors its action runs opposite to that of agouti-related peptide, an endogenous antagonist and inverse agonist. The lactam ring is thought to hold the core residues in a turn conformation that favours receptor binding.

Molecular Information

  • Type: Cyclic heptapeptide (α-MSH analog)
  • Length: 7 amino acids
  • 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-associated melanoma

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

    PMID 21564053 — 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