1. Identity and structure
| Property | Detail |
|---|---|
| Names | Melanotan-2, Melanotan II, MT-II |
| Sequence | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 |
| Ring | Lactam bridge between Asp and Lys side chains |
| Approx. molecular weight | ≈1,024 Da |
| Parent | α-MSH (13 residues) |
2. Development
Melanotan-2 was developed in the late 1980s and early 1990s at the University of Arizona by the groups of Victor Hruby and Mac Hadley. It was derived from the linear analog Melanotan-1 (afamelanotide) by shortening the sequence and closing a lactam ring, which constrains the His-D-Phe-Arg-Trp core — the minimal binding motif shared by melanocortin ligands — and increases resistance to proteases.
3. The melanocortin receptor family
| Receptor | Main endogenous ligand(s) | Typical location |
|---|---|---|
| MC1R | α-MSH | Melanocytes |
| MC2R | ACTH only | Adrenal cortex |
| MC3R | γ-MSH, α-MSH | Brain and periphery |
| MC4R | α-MSH | Brain |
| MC5R | α-MSH | Exocrine glands |
All five are class A G-protein-coupled receptors that signal through Gs and cAMP. Melanotan-2 is a non-selective agonist at MC1R, MC3R, MC4R and MC5R, and does not activate MC2R.
4. The MC1R–MITF axis
In melanocytes, MC1R activation raises cAMP, activates protein kinase A and the transcription factor CREB, and increases expression of MITF, the master regulator of melanogenesis genes such as tyrosinase. Abdel-Malek and colleagues reviewed the role of MC1R in the melanocyte UV response; Xu et al. (2025) and Pucci et al. (2012) studied other inputs into the same melanogenesis pathway.
5. Analytical characterization
Identity and purity are confirmed analytically for every lot. Reversed-phase HPLC with UV detection quantifies chromatographic purity, and electrospray mass spectrometry (ESI-MS) confirms that the observed molecular mass matches the theoretical value for Melanotan-2.
Results are reported on a lot-specific certificate of analysis together with appearance, net content and the lot number, which allows any vial to be traced back to its analytical record.
6. Storage and handling
Material is supplied as a lyophilized solid in a sealed vial. Unopened vials are best kept at −20 °C, protected from light and moisture. Allow a vial to equilibrate to room temperature before opening to limit condensation, and record the lot number so the vial can be matched to its certificate of analysis.
A lot-specific certificate of analysis is available for each batch.
Sources
- Abdel-Malek ZA, Knittel J, Kadekaro AL, et al. The melanocortin 1 receptor and the UV response of human melanocytes–a shift in paradigm. Photochem Photobiol. 2008. doi:10.1111/j.1751-1097.2008.00294.x. PMID: 18282187. PubMed.
- Xu M, Zhang Z, Zhang P, et al. Disrupting the MC1R/α-MSH-pCREB-MITF Axis: Rhein-based PROTAC D16 as a Potent Melanogenesis Inhibitor. Chem Biodivers. 2025. doi:10.1002/cbdv.202501651. PMID: 40779718. PubMed.
- Pucci M, Pasquariello N, Battista N, et al. Endocannabinoids stimulate human melanogenesis via type-1 cannabinoid receptor. J Biol Chem. 2012. doi:10.1074/jbc.M111.314880. PMID: 22431736. PubMed.
Research Use Only. All products sold by ShortChain Aminos are intended strictly for laboratory research purposes. They are not for human or veterinary use, and nothing in this article constitutes medical advice, usage instructions, or a recommendation of any kind. This content summarizes published third-party research for informational purposes only.