Melanotan II (MT-II) is a synthetic cyclic heptapeptide analogue of α-melanocyte stimulating hormone (α-MSH). Originally developed at the University of Arizona in the 1980s as a candidate photoprotective compound, it is a non-selective agonist across the melanocortin receptor family. The “pathways mapped” element is what distinguishes serious research literature from popular framing.
Sequence and structure
Melanotan II: Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-NH₂. The cyclic backbone (lactam bridge between Asp² and Lys⁷) confers protease resistance and locks the peptide in an active receptor-binding conformation.
The melanocortin receptor family
Five G-protein-coupled receptors comprise the melanocortin family: MC1R, MC2R, MC3R, MC4R, and MC5R. Each has a distinct tissue distribution and physiological role.
| Receptor | Tissue distribution | Primary function (research) |
|---|---|---|
| MC1R | Melanocytes | Eumelanin synthesis (skin pigmentation) |
| MC2R | Adrenal cortex | Cortisol release (ACTH-driven) |
| MC3R | Hypothalamus, immune cells | Energy homeostasis, inflammation |
| MC4R | CNS, hypothalamus | Appetite, sexual function, autonomic tone |
| MC5R | Exocrine glands, immune cells | Sebaceous secretion, sweat regulation |
Melanotan II’s binding profile
MT-II is non-selective — it activates MC1R, MC3R, MC4R, and MC5R with comparable potency, while MC2R activation requires the larger ACTH peptide. The non-selectivity is precisely what makes MT-II useful as a research probe but limits its therapeutic specificity.
MC1R and melanogenesis research
The MC1R pathway is the most-studied. Activation triggers adenylyl cyclase, raises intracellular cAMP, and upregulates microphthalmia-associated transcription factor (MITF). MITF drives expression of tyrosinase and related enzymes that produce eumelanin. Research models confirm that MC1R activation increases melanin output independent of UV exposure — a key finding in the original photoprotection research programme.
MC4R pathway — appetite and central effects
MC4R activation in hypothalamic nuclei reduces food intake and increases energy expenditure in research models. This is the same receptor that setmelanotide (a selective MC4R agonist) targets in clinical obesity research. MT-II’s MC4R activation is part of why appetite suppression is reported in research animals — but the non-selectivity makes it a blunt tool compared to setmelanotide.
MC3R and inflammation
MC3R is expressed in macrophages and other immune cells. Research suggests MC3R activation downregulates pro-inflammatory cytokine release. The pathway is less well characterised than MC1R or MC4R but is an active area of melanocortin research.
MC5R and exocrine function
MC5R activation in sebaceous and exocrine tissues alters secretory function. Less central to most MT-II research but documented.
Stability and reconstitution
MT-II is supplied lyophilised. Reconstitution in bacteriostatic water at 1–2 mg/mL is standard. The cyclic backbone confers good stability — refrigerated reconstituted MT-II retains potency for approximately 4 weeks. Protect from light to prevent photodegradation of the tryptophan residue.
Open research questions
- Long-term receptor desensitisation across the melanocortin family
- Tissue-specific selectivity strategies (MT-II vs Setmelanotide vs PT-141)
- Interaction effects when multiple MC receptors are activated simultaneously
Chempeptides supplies HPLC-verified Melanotan II with batch CoA — see the research catalogue. Research use only.