Melanotan II
[CAS# 121062-08-6]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Other protected amino acids
• Name: Melanotan II
• Synonyms: N-Acetyl-L-norleucyl-L-alpha-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-lysinamide (2->7)-lactam; Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2; Ac-[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH-(4-10)-NH2
• Molecular Formula: C₅₀H₆₉N₁₅O₉
• Molecular Weight: 1024.18
• CAS Registry Number: 121062-08-6
• SMILES: CCCC[C@@H](C(=O)N[C@H]1CC(=O)NCCCC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@@H](NC1=O)CC2=CN=CN2)CC3=CC=CC=C3)CCCN=C(N)N)CC4=CNC5=CC=CC=C54)C(=O)N)NC(=O)C

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Solubility: Soluble 0.70 mg/mL (water) (Expl.)
• Index of refraction: 1.683 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

Melanotan II is a synthetic cyclic peptide analogue of the naturally occurring α-melanocyte-stimulating hormone (α-MSH), which is part of the melanocortin peptide family. It was developed to mimic the biological activity of α-MSH, primarily by binding to melanocortin receptors, particularly MC1R and MC4R, to induce pigmentation and influence appetite and sexual function. The cyclic structure of Melanotan II enhances its stability against enzymatic degradation, allowing for prolonged activity compared to the endogenous hormone.

The discovery of Melanotan II traces back to research on the physiological effects of melanocortins, which regulate skin pigmentation, energy homeostasis, and sexual behavior. Early studies demonstrated that α-MSH could increase melanin production in melanocytes, leading to protective tanning effects. However, the natural hormone had limited clinical utility due to rapid metabolism. Researchers synthesized Melanotan II to achieve increased potency, extended half-life, and targeted receptor specificity while reducing unwanted side effects.

Melanotan II primarily acts on the MC1R receptor in melanocytes, stimulating melanogenesis and increasing skin pigmentation without direct exposure to ultraviolet radiation. This property has led to interest in its potential as a pharmacological tanning agent to reduce the risk of UV-induced skin damage. In addition to its effects on pigmentation, Melanotan II interacts with MC4R in the hypothalamus, modulating appetite and sexual arousal. Preclinical studies and early human trials have shown that Melanotan II can induce spontaneous erections, enhance libido, and reduce food intake, demonstrating the pleiotropic effects of melanocortin receptor activation.

Pharmacokinetically, Melanotan II is typically administered via subcutaneous injection. Its cyclic peptide structure ensures slow enzymatic degradation, allowing measurable systemic effects after a single dose. Adverse effects observed in clinical studies include nausea, flushing, and temporary changes in blood pressure. Long-term safety data remain limited, and its use is generally restricted to research settings or under controlled clinical protocols. Regulatory approval varies by country, and it is not broadly approved for cosmetic or therapeutic use.

Beyond pigmentation and sexual function, research into Melanotan II has explored potential roles in obesity management, due to its appetite-suppressing effects mediated through central melanocortin pathways. The peptide has also served as a model compound for developing selective melanocortin receptor agonists with improved efficacy and reduced side effects. Its design exemplifies rational peptide engineering, where modifications to endogenous hormone structures can optimize pharmacological properties while maintaining receptor specificity.

Overall, Melanotan II represents a synthetic melanocortin analogue with multiple biological activities, most notably in pigmentation and sexual function. Its development illustrates the translation of basic hormone biology into peptide therapeutics and provides insights for the design of selective receptor-targeted drugs with diverse physiological effects.

References

Wessells H, Levine N, Hadley ME, Dorr R, Hruby VJ (2000) Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. International Journal of Impotence Research 12 Suppl 4 S74–S79 DOI: 10.1038/sj.ijir.3900582

Dorr RT, Hadley ME, Shilkaitis A, Johnson DA, Blaustein JB (1996) Evaluation of melanotan‑II, a superpotent cyclic melanotropic peptide in a pilot phase‑I clinical study. Life Sciences 58 (20) 1777–1784 DOI: 10.1016/0024‑3205(96)00160‑9

Breindahl T, Evans‑Brown M, Hindersson P, McVeigh J, Bellis M, Stensballe A, Kimergård A (2014) Identification and characterization by LC‑UV‑MS/MS of melanotan II skin‑tanning products sold illegally on the Internet. Drug Testing and Analysis 6(2) 164–172 DOI: 10.1002/dta.1655