FDA-approved photoprotection from within
A linear α-MSH analog that selectively activates MC1R to drive photoprotective pigmentation.
Educational content. This page describes Melanotan 1 (Afamelanotide) for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
In the pivotal Phase III trial, patients with erythropoietic protoporphyria gained a median 69.4 hours of pain-free sun exposure versus 40.8 hours with placebo over 180 days.[1]
Afamelanotide, also known as Melanotan 1, is a synthetic 13-amino-acid linear analog of alpha-melanocyte-stimulating hormone. Its chemical designation is [Nle4, D-Phe7]-alpha-MSH, reflecting two key substitutions: norleucine replaces methionine at position 4 (preventing oxidative degradation) and D-phenylalanine replaces L-phenylalanine at position 7 (conferring protease resistance). These modifications make it 10 to 1,000 times more potent than native alpha-MSH with a much longer duration of action.
Afamelanotide is the first and only melanocortin-1 receptor agonist approved for therapeutic use. The FDA approved it in October 2019 under the brand name Scenesse for increasing pain-free light exposure in adults with erythropoietic protoporphyria (EPP), a rare genetic disorder where accumulated protoporphyrin IX causes severe phototoxic pain upon light exposure. The EMA had previously approved it in 2014. It is manufactured by Clinuvel Pharmaceuticals as a 16 mg biodegradable subcutaneous implant.
Afamelanotide binds selectively to MC1R on the surface of melanocytes. This activates the Gs protein/adenylyl cyclase/cAMP/PKA signaling cascade, which phosphorylates CREB and upregulates MITF (microphthalmia-associated transcription factor). MITF then drives expression of tyrosinase, TRP-1, and TRP-2, the enzymes responsible for eumelanin synthesis. The resulting brown/black eumelanin is deposited in the epidermis where it absorbs UV radiation and scavenges free radicals.
Beyond pigmentation, MC1R/cAMP signaling activates a DNA repair pathway that operates independently of melanin production. PKA phosphorylates ATR (ataxia telangiectasia and Rad3-related protein) at serine 435, which enhances its binding with XPA, a critical nucleotide excision repair factor. This accelerates removal of cyclobutane pyrimidine dimers and 6-4 photoproducts from damaged DNA. The effect occurs even in melanocytes that lack tyrosinase.
In EPP patients specifically, the increased eumelanin layer absorbs visible light wavelengths that would otherwise excite accumulated protoporphyrin IX in the skin. By reducing photon absorption by protoporphyrin, afamelanotide decreases the painful phototoxic reactions that confine these patients indoors.
FDA-approved photoprotection from within
Afamelanotide selectively activates MC1R on melanocytes, driving eumelanin synthesis through the cAMP/PKA/CREB/MITF cascade and simultaneously enhancing nucleotide excision repair through ATR phosphorylation and XPA recruitment. It does not cross the blood-brain barrier meaningfully, so it lacks the central nervous system effects (sexual, appetite) seen with Melanotan 2.
Key studies supporting the therapeutic use of this peptide.
US study: median pain-free sun exposure 69.4 hours with afamelanotide versus 40.8 hours with placebo (p = 0.04). EU study: 6.0 versus 0.8 hours (p = 0.005). Phototoxic reactions reduced from 146 to 77 (p = 0.04). No drug-related serious adverse events.
Langendonk JG, Balwani M, Anderson KE, et al. — N Engl J Med, 373(1):48-59 (2015) · PubMed
Three 10-day cycles of subcutaneous afamelanotide at 0.16 mg/kg over 3 months increased melanin density by up to 41%. Sunburn cells were reduced by more than 50%. Thymine dimer formation in the basal layer was reduced by 59% (p = 0.002).
Barnetson RS, Ooi TK, Zhuang L, et al. — J Invest Dermatol, 126(8):1869-1878 (2006) · PubMed
Combination of NB-UVB plus monthly 16 mg afamelanotide implants achieved 48.6% repigmentation versus 33.3% for NB-UVB alone by day 168. Face repigmentation was faster (41 versus 61 days, p = 0.001). Response was stronger in darker skin types.
Lim HW, Grimes PE, Agbai O, et al. — JAMA Dermatol, 151(1):42-50 (2015) · PubMed
Alpha-MSH activated the PI3K/Akt pathway, enhanced cyclobutane pyrimidine dimer repair, and reduced hydrogen peroxide levels through MC1R. Anti-apoptotic effects were independent of melanin synthesis and absent in MC1R-deficient melanocytes.
Kadekaro AL, Kavanagh R, Kanto H, et al. — Cancer Res, 65(10):4292-4299 (2005) · PubMed
Typical protocols used in clinical practice. Always consult a licensed provider for personalized dosing.
Subcutaneous Implant (FDA-Approved)
Subcutaneous Injection (Research)
Subcutaneous Implant (FDA-Approved): Implanted above the anterior supra-iliac crest by a trained healthcare professional. Over 90% released by day 5; plasma undetectable by day 10.
Subcutaneous Injection (Research): Used in the Barnetson 2006 study. The implant formulation replaced injectable protocols for clinical use.
Scenesse is available only through a restricted program and must be administered by a healthcare professional. It is not a self-administered medication.
The implant delivers controlled release over approximately 5 days, with an apparent half-life of about 15 hours from the implant depot. The free peptide half-life is approximately 30 minutes.
Patients should undergo full-body skin examination twice yearly to monitor for changes in moles, new pigmented lesions, and freckle development.
Afamelanotide has been studied in multiple Phase II and III randomized controlled trials with a well-characterized safety profile. No drug-related serious adverse events were identified in the pivotal EPP trials. A post-authorization safety study of 200 patients confirmed long-term safety with no new signals.
The primary safety consideration is melanocytic change. New moles were reported at twice the placebo rate in clinical trials, though no melanoma progression was documented. Twice-yearly full-body skin examinations are recommended during treatment.
Because afamelanotide is MC1R-selective and does not meaningfully cross the blood-brain barrier, it lacks the central nervous system side effects (sexual arousal, appetite suppression, severe nausea) associated with the non-selective Melanotan 2.
See how Melanotan 1 (Afamelanotide) compares to peptides with overlapping benefits.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Melanotan 1 (Afamelanotide) | Photoprotection & Pigmentation | Subcutaneous Implant | Every 60 days (ongoing) | The only FDA-approved melanocortin agonist, combining eumelanin induction with UV-independent DNA repair through a selective MC1R mechanism |
| Melanotan 2 | Pigmentation & Sexual Function | Injection | 2 weeks (clinical trial protocol) | Non-selective melanocortin agonist producing simultaneous tanning, sexual arousal, and appetite suppression, but with significant safety concerns that prevented regulatory approval |
| AHK-Cu | Hair & Skin Regeneration | Topical | 8 to 12 weeks | Hair follicle-focused copper peptide with demonstrated dermal papilla cell protection and a biphasic dose response requiring precise formulation |
Current FDA classification and compounding eligibility.
This peptide is an FDA-approved drug available via standard prescription.
FDA-approved as Scenesse for erythropoietic protoporphyria (EPP). Subcutaneous implant every 2 months. Approved for the narrow indication of photoprotection in EPP patients.
FDA approved Scenesse (afamelanotide 16 mg implant) to increase pain-free light exposure in adults with EPP
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
Harms J, Lautenschlager S, Minder EI, Minder CE “An alpha-melanocyte-stimulating hormone analogue in erythropoietic protoporphyria.” N Engl J Med, 360(3):306-307 (2009)
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