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Explore  /  Afamelanotide (Scenesse / Melanotan-1)
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Afamelanotide (Scenesse / Melanotan-1)

A
lead outcome
EPP — phototoxicity prevention / pain-free…
grades vary by outcome ↓
Peptide
also called — Afamelanotide · trade name Scenesse (Clinuvel) · Melanotan-1 / Melanotan I / MT-1 (the research-peptide name) · [Nle⁴, D-Phe⁷]-α-MSH (NDP-MSH) · CUV-1647
(approved:) photoprotection / EPP phototoxicity-preventionMC1R-driven eumelanin synthesis(gray-market, as "Melanotan-1":) cosmetic tanning

The approved melanocortin — and the anchor that closes the register's melanocortin trio. Three points make this entry land: (1) it is a genuinely FDA- and EMA-approved drug (Scenesse) — a first-in-class rare-disease therapy — for erythropoietic protoporphyria; (2) it is chemically identical to the g

In brief

Afamelanotide is a synthetic α-MSH analog and selective MC1R agonist — and a genuinely approved, first-in-class drug (Scenesse, EMA 2015 / FDA 2019) for the rare disease erythropoietic protoporphyria (EPP), where a ferrochelatase defect causes protoporphyrin IX to build up and makes sunlight excruciatingly painful. By activating MC1R, it drives eumelanin (brown-black pigment) production independent of UV exposure, plus antioxidant and DNA-repair effects — letting EPP patients tolerate far more light: in Phase 3, patients on afamelanotide spent ~64 hours in direct sunlight pain-free over 180 days vs ~41 on placebo. The twist that matters for this register: afamelanotide is chemically identical to the gray-market "Melanotan-1," and its MC1R-selectivity is exactly what separates it from its two famous cousins — Melanotan II (#32), a non-selective analog that also hits MC3R/MC4R/MC5R (hence tanning plus appetite/libido/side-effects), and PT-141/bremelanotide (#46), an MC4R-selective analog approved for sexual desire. One α-MSH family, three receptor-selectivity profiles, three completely different destinies — approved-for-skin, unapproved-and-broad, approved-for-sex.

Legal standing, by region
International
approved in Australia (TGA)

approved in Australia (TGA); available for EPP in various markets.

Evidence, by outcome

An honest grade per outcome — drawn from the evidence, not any catalogue. Hype and undemonstrated marketing claims grade low.

OutcomeEvidence base · effectGrade
EPP — phototoxicity prevention / pain-free light exposure (the approved use)
Approved, first-in-class for a genuine unmet need — but for an ultra-rare disease; effect is meaningful-but-modest (extra tolerated-light hours), not a cure; EU approval under exceptional circumstances
3 randomized vehicle-controlled Phase 3 trials (CUV029/030/039, 244 adults) → EMA 2015 + FDA 2019; ~64 vs ~41 pain-free sunlight hours/180 days
A
UV-independent skin pigmentation (eumelanin)
The core mechanism is real and reproducible; it is what the drug does
Robust, well-characterised pharmacology (MC1R → eumelanogenesis)
B
Cosmetic tanning (the gray-market "Melanotan-1" use)
The pathway works, but it's unapproved for cosmetics, uses an injectable systemic drug for vanity, and gray-market product quality is unverified; approved-disease data don't transfer to cosmetic safety
Mechanistically works (same eumelanin pathway); no approval for this indication
D
Other explored uses (vitiligo, PLE, solar urticaria, acne)
Mostly unpublished or not pursued; vitiligo saw some further work; not established
Early Clinuvel trials 2007-2011
D
Photoprotection in the general (non-EPP) population
The EPP approval is disease-specific; it is not a general "safe tanning / sun-protection" drug
Not an approved or established use
F
Safety
Implant-site reactions, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevi (new/changing moles). A theoretical melanoma risk → full-body skin exam twice yearly is recommended; MC1R-selectivity gives it a cleaner systemic profile than Melanotan II
Approval-grade dataset (244 patients + post-marketing)

Identity a synthetic linear 13-amino-acid peptide (tridecapeptide) analog of α-melanocyte-stimulating hormone (α-MSH), engineered as a potent, selective agonist of the melanocortin-1 receptor (MC1R) — the receptor on skin melanocytes that controls pigment. Developed by Clinuvel Pharmaceuticals. Critically, afamelanotide is the same molecule sold on the gray market as "Melanotan-1" — but here as a pharmaceutical-grade, controlled-release implant. ## Mechanism (as proposed) afamelanotide is a potent, MC1R-selective α-MSH analog (MC1R affinity ~0.3 nM, roughly 1,000× lower at MC3R/MC4R). MC1R sits on melanocytes; activating it shifts pigment synthesis toward eumelanin (brown-black, photoprotective) over pheomelanin, and does so without UV (bypassing the DNA-damage step that normal tanning requires). MC1R signalling also induces antioxidant activity, enhances DNA repair, and modulates inflammation — which is why, in EPP, more eumelanin plus these ancillary effects absorb/scatter light and blunt the protoporphyrin-IX phototoxic reaction. The Nle⁴/D-Phe⁷ substitutions are what give it the potency and metabolic stability the native hormone lacks.

Sources — 5 cited
01SCENESSE (afamelanotide) FDA label + FDA approval (Oct 2019, first-in-class); EMA authorisation (2015, exceptional circumstances).
02Sawyer TK, et al. [Nle⁴,D-Phe⁷]-α-MSH: a highly potent α-melanotropin with ultralong biological activity. PNAS. 1980 (the molecule's origin).
03Phase 3 EPP trials (CUV029, CUV030, CUV039); Medscape/NEJM-reported outcomes (~64 vs ~41 pain-free sunlight hours).
04Wensink D, et al. Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Expert Rev Clin Pharmacol. 2021 (review).
05Comparative melanocortin pharmacology (MC1R vs MC4R selectivity) — afamelanotide vs Melanotan II vs bremelanotide.
Review status
Not yet reviewed

A credentialed reviewer (PharmD / PhD / MD) will be named before this entry is finalised. Until then, treat it as a working draft. Last updated July 2026 (approval status stable; note ongoing post-marketing safety surveillance and any label/indication changes).

Grades reflect the published evidence, not our interest. No dosing, reconstitution, or administration is published for research compounds — that restraint is deliberate.

Related compounds
Melanotan IIC
Peptide
PT-141 (Bremelanotide)B
Peptide
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Afamelanotide (Scenesse) — the approved MC1R agonist: the same molecule as Melanotan-1, the honest evidence · Vallydia