Melanotan-I vs Melanotan-II: Melanocortin Peptide Research Comparison
Published: 2026-03-19Updated: 2026-03-19Category: Comparisons
Melanotan-I (afamelanotide) and Melanotan-II are both synthetic analogues of alpha-melanocyte stimulating hormone (α-MSH), but they differ significantly in receptor selectivity, structure, and research applications. This guide compares the published preclinical and clinical research on each.
Structural Overview
| Property | Melanotan-I | Melanotan-II |
|---|
| Full Name | Afamelanotide / [Nle4, D-Phe7]-α-MSH | Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 |
| Structure | Linear tridecapeptide (13 amino acids) | Cyclic heptapeptide (7 amino acids) |
| Receptor Selectivity | MC1R selective | Non-selective MC1R/MC3R/MC4R/MC5R |
| CAS Number | 75921-69-6 | 121062-08-6 |
| Regulatory Status | EU-approved (Scenesse) for EPP | Not approved — research compound |
Mechanism of Action
Melanotan-I (Afamelanotide)
Melanotan-I is a full-length linear analogue of α-MSH with selective binding to the MC1R melanocortin receptor. MC1R activation stimulates eumelanin production in melanocytes via the cAMP/PKA signaling cascade. The Nle4 and D-Phe7 substitutions increase receptor binding affinity and enzymatic stability compared to native α-MSH. Afamelanotide received European regulatory approval in 2014 under the brand name Scenesse for adult patients with erythropoietic protoporphyria (EPP).
Melanotan-II
Melanotan-II is a cyclic heptapeptide that binds non-selectively across multiple melanocortin receptor subtypes (MC1R through MC5R). This broader receptor profile means that in addition to melanogenesis via MC1R, Melanotan-II has been studied for MC3R/MC4R-mediated effects in preclinical models. The cyclic structure provides greater enzymatic stability than linear peptides. PT-141 (Bremelanotide), an FDA-approved drug, was derived from Melanotan-II research.
Key Research Differences
| Research Area | Melanotan-I | Melanotan-II |
|---|
| Melanogenesis | Primary focus — MC1R-selective eumelanin production | Also stimulates melanogenesis but via broader receptor activation |
| Receptor selectivity | MC1R only | MC1R, MC3R, MC4R, MC5R |
| Photoprotection research | Extensive clinical data — EU approval for EPP | Preclinical data only for photoprotection |
| MC4R-mediated effects | Minimal — low MC4R affinity | Significant — studied in appetite and sexual function models |
| Clinical trials | Phase III completed (EPP) | Not progressed to late-stage clinical trials as a drug |
Published Study Highlights
Melanotan-I: Langendonk et al. (2015) published the pivotal Phase III trial for afamelanotide in EPP patients. Lim et al. (2005) demonstrated increased melanin density and reduced UV sensitivity in healthy volunteers. Multiple dermatological studies have confirmed MC1R-mediated photoprotective effects.
Melanotan-II: Dorr et al. (1996) published early human volunteer studies demonstrating melanogenic effects. Hadley and Dorr (2006) reviewed the broader melanocortin receptor pharmacology. PT-141, a metabolite derivative, was subsequently developed and FDA-approved in 2019 as Vyleesi.
Important distinction: Melanotan-I has a defined regulatory pathway (EU-approved for EPP). Melanotan-II has no regulatory approval in any jurisdiction and is available solely as a research chemical reference material. Both are available at Pepta Labs for in-vitro research use only.
Availability
Both melanocortin peptides are available at Pepta Labs with ≥99% HPLC purity and independent third-party COA: Melanotan-I 10mg | Melanotan-II 10mg. Download COAs directly from each product page.
All information is sourced from published peer-reviewed literature and provided for educational purposes only. This content does not represent claims about products sold by Pepta Labs. All products are chemical reference materials for in-vitro laboratory research only. Not for human or animal consumption. See
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