Melanotan II

About Melanotan II

Melanotan II is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (α-MSH), the hormone that signals melanocytes to produce pigment. It was designed in the 1980s by Victor Hruby's group at the University of Arizona, which was searching for α-MSH analogues stable enough to be useful as research tools and, potentially, as sunless-tanning agents. Replacing the L-phenylalanine of α-MSH with D-phenylalanine and closing the ring with a lactam bridge produced a molecule far more potent and longer-acting than the natural hormone.

Melanotan II is a non-selective agonist: it activates the MC1, MC3, MC4 and MC5 melanocortin receptors. That breadth is why early clinical studies in the 1990s recorded effects well beyond pigmentation, and why its des-amide metabolite was later developed separately as bremelanotide. Development of Melanotan II itself as a medicine was abandoned; it is not approved for any use in any country, and regulators including Health Canada have warned specifically against unauthorised injectable melanotan products.

In the laboratory it is used as a reference melanocortin agonist in studies of MC1R signalling and melanogenesis in melanocytes, of MC4R-mediated energy homeostasis and, in comparison with selective analogues, of receptor-subtype pharmacology.

Mechanism

Melanocortin receptors are G-protein-coupled receptors that raise intracellular cAMP when activated. In melanocytes, MC1R activation drives the microphthalmia-associated transcription factor (MITF) and the enzyme tyrosinase, increasing eumelanin synthesis. MC4R, expressed in the hypothalamus, regulates appetite and energy balance; MC3R and MC5R are involved in energy homeostasis and exocrine function respectively. Because Melanotan II activates all four, it is a tool for studying the system as a whole rather than one receptor.

Areas of research

1. Non-selective agonist at the MC1, MC3, MC4 and MC5 melanocortin receptors
2. Reference agonist in studies of MC1R signalling and melanin synthesis in melanocytes
3. Studied in MC4R-mediated pathways of appetite and energy homeostasis
4. Parent compound of bremelanotide, its des-amide metabolite developed separately

References

1. Dorr RT et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a single-dose clinical study. Life Sci. 1996;58(20):1777-1784. PubMed
2. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-930. PubMed
3. Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017;56(10):975-980. PubMed

Research use only. Information on this page is provided for educational and research purposes and summarises published literature, mostly from cell and animal studies; it is not a claim of efficacy or safety. Products are not intended for human or veterinary use, or for any diagnostic or therapeutic purpose.