Melanotan II

Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that activates several melanocortin receptors. It is not approved as a medicine anywhere, and regulators have warned about unlicensed tanning products.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Melanotan II was developed at the University of Arizona in the late 1980s and 1990s, as part of research into synthetic analogues of alpha-melanocyte-stimulating hormone (α-MSH) that might stimulate skin pigmentation. Its cyclic structure made it more potent and longer-lasting than the natural hormone. Early small human studies reported skin darkening and also unexpected effects on sexual arousal, which led to the development of the related compound bremelanotide.

Melanotan II itself has not been approved as a medicine by the FDA or by any other regulator. Despite this, it has been widely sold online as an unlicensed tanning product. Regulators including the FDA, the UK Medicines and Healthcare products Regulatory Agency (MHRA) and Australia's Therapeutic Goods Administration (TGA) have issued warnings about such products, citing unknown quality and safety. Research interest continues in the melanocortin system more broadly.

Compare: PT-141 vs Melanotan II, Afamelanotide vs Melanotan II.

Structure

Melanotan II is a cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2. It is cyclized through a lactam bridge between the side chains of aspartic acid and lysine, includes norleucine and D-phenylalanine, is acetylated at the N-terminus and amidated at the C-terminus. It is closely related to bremelanotide, which has a free C-terminal acid instead of an amide. The His-D-Phe-Arg-Trp core is the conserved melanocortin pharmacophore, and the tryptophan is oxidation-prone.

Mechanism

Melanotan II is a non-selective agonist at melanocortin receptors. Activation of MC1R on melanocytes stimulates melanin production, which explains its pigmentation effects. Activation of MC3R and MC4R in the brain is linked to effects on sexual arousal and appetite observed in animal and early human studies. Because the peptide acts on several receptor subtypes, its effects are broad. Its lack of selectivity is one reason it was not developed as a medicine, while more targeted analogues were pursued.

Research

Pigmentation studies

Early research at the University of Arizona examined melanotan II and related analogues for their ability to induce skin pigmentation, partly as a possible approach to photoprotection. Small human studies reported increased pigmentation. These studies were small and early-stage, and melanotan II did not proceed to approval. The related analogue afamelanotide, a linear α-MSH analogue, was later developed for a specific photosensitivity disorder.

Sexual function and the origin of bremelanotide

Small early clinical studies of melanotan II in men reported effects on erectile function, which drew attention to central melanocortin pathways in sexual behavior. This observation led directly to the development of bremelanotide (PT-141), which was later approved for hypoactive sexual desire disorder in women. Melanotan II itself was not taken forward. The two compounds differ only at the C-terminus.

Safety concerns and case reports

Because melanotan II has been used outside medical supervision, the literature includes case reports of adverse events associated with unlicensed products, including changes in existing moles and other dermatological findings. Case reports cannot establish cause, and product contents are often unknown. These reports underpin regulatory warnings and highlight the absence of controlled safety data. Controlled long-term human safety studies have not been published.

Appetite and energy balance research

In animal studies, melanotan II has been used as a research tool to activate central melanocortin receptors involved in appetite and energy balance, particularly MC4R. These experiments helped clarify the role of the melanocortin system in feeding behavior. They are animal findings and do not support use of melanotan II in people. Its broad receptor activity makes it a blunt research tool.

Regulatory status

Melanotan II is not approved as a medicine by the FDA or by any other regulator. Regulators including the FDA, the UK MHRA and Australia's TGA have warned the public about unlicensed tanning products marketed as melanotan, noting that their safety, quality and contents are unknown. It is handled in research settings as a laboratory tool compound. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A melanotan II certificate of analysis should confirm identity by mass spectrometry against the expected mass shown on this page and report HPLC purity. A key pitfall is distinguishing melanotan II from bremelanotide, which differs only by a C-terminal amide versus acid, about 1 Da; high-resolution MS and a reference standard help. Incomplete cyclization produces a linear species with a +18 Da mass. Tryptophan oxidation and D-Phe epimerization should be considered. Salt form and net peptide content should be reported.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized melanotan II sealed at -20 °C, protected from light and moisture. The tryptophan residue is sensitive to light and oxidation, so light shielding is advisable. The cyclic lactam structure confers better stability than many linear peptides, but solutions should still be aliquoted, kept cold and not subjected to repeated freeze-thaw cycles.

Download the Melanotan II data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• PT-141 (bremelanotide)

  PT-141, or bremelanotide, is a cyclic heptapeptide melanocortin receptor agonist derived from melanotan II. It was FDA-approved in 2019 as Vyleesi for hypoactive sexual desire disorder in premenopausal women.

• Kisspeptin-10

  Kisspeptin-10 is the C-terminal decapeptide of kisspeptin, the product of the KISS1 gene. It activates the kisspeptin receptor (KISS1R, also called GPR54) and is studied as a regulator of gonadotropin-releasing hormone and reproductive hormones.

• Oxytocin

  Oxytocin is a nine-amino-acid peptide hormone made in the hypothalamus and released from the posterior pituitary, with a disulfide-bridged ring structure. It regulates uterine contraction and milk ejection, and synthetic oxytocin (Pitocin) is FDA-approved.

References

1. PubMed: all indexed literature on Melanotan II
2. ClinicalTrials.gov: registered studies mentioning Melanotan II