Melanotan 1 (Afamelanotide) vs Melanotan II
Melanotan 1 (afamelanotide) and Melanotan II are both synthetic analogs of alpha-melanocyte-stimulating hormone developed at the University of Arizona, but they diverged sharply: Melanotan 1 is a linear, MC1R-focused peptide that became an approved drug, while Melanotan II is a smaller cyclic analog with broad receptor activity.
Side-by-Side Comparison
| Property | Melanotan 1 (Afamelanotide) | Melanotan II |
|---|---|---|
| Category | Linear alpha-MSH analog ([Nle4, D-Phe7]-alpha-MSH, 13 amino acids) | Cyclic lactam alpha-MSH analog (7 amino acids) |
| Mechanism of Action | Potent MC1R agonist; stimulates eumelanin synthesis in melanocytes (photoprotective pigmentation) | Non-selective agonist at MC1R, MC3R, MC4R, MC5R; produces pigmentation plus central melanocortin effects |
| Molecular Weight | ~1,647 Da | ~1,024 Da |
| Primary Research Focus | Photoprotection; approved (Scenesse) for erythropoietic protoporphyria (EPP) | Pigmentation, appetite, and CNS melanocortin pathway research |
| Receptor Target | MC1R (primary) | MC1R, MC3R, MC4R, MC5R (non-selective) |
| Half-Life | ~30 minutes (clinical use employs a sustained-release implant) | ~1-2 hours (estimated) |
| Key Research Citations | Langendonk et al. (2015), NEJM; Hadley & Dorr (2006), Peptides | Dorr et al. (1996), Life Sci; Wessells et al. (1998), J Urol |
Key Differences
- Melanotan 1 is a linear 13-amino-acid peptide focused on MC1R; Melanotan II is a truncated cyclic heptapeptide active across four melanocortin receptors.
- Melanotan 1 became a regulated pharmaceutical: as afamelanotide (Scenesse) it holds approval for erythropoietic protoporphyria. Melanotan II never advanced to approval.
- Melanotan II’s MC3R/MC4R activity produces central effects (appetite suppression, sexual function signals) that MC1R-focused Melanotan 1 largely lacks; that same activity made Melanotan II the structural parent of PT-141.
- Melanotan 1’s clinical delivery uses a sustained-release implant to offset its short half-life; Melanotan II research uses conventional parenteral protocols.
Research Summary
Melanotan 1 and Melanotan II started from the same alpha-MSH scaffold and split into two research lineages. Melanotan 1 (afamelanotide) kept the linear structure, concentrated its activity on MC1R-driven photoprotective pigmentation, and progressed to regulatory approval for EPP. Melanotan II, a compact cyclic analog, trades selectivity for breadth: it engages MC1R through MC5R, producing both pigmentation and central melanocortin effects, and served as the structural starting point for the MC4R-focused PT-141.
What is the difference between Melanotan 1 and Melanotan II?
Melanotan 1 (afamelanotide) is a linear 13-amino-acid alpha-MSH analog selective for MC1R, studied for photoprotective pigmentation and approved as Scenesse for erythropoietic protoporphyria. Melanotan II is a smaller cyclic analog that activates MC1R through MC5R non-selectively, producing pigmentation plus central effects, and is the structural parent of PT-141.
More Comparisons
Disclaimer: All compounds referenced on this page are sold for research and laboratory use only. The comparisons presented are based on published scientific literature and are intended for educational and informational purposes. This content does not constitute medical advice. Researchers should consult primary literature and applicable regulations before designing study protocols.