Melanotan I (Afamelanotide)
approvedAlso known as: Afamelanotide, Scenesse, MT-1
**Mechanism of Action** Melanotan I (afamelanotide) is a synthetic tridecapeptide analog of α-melanocyte-stimulating hormone (α-MSH) that acts as a selective agonist at the melanocortin-1 receptor (MC1R). Activation of MC1R on melanocytes stimulates the cAMP-dependent signaling pathway, leading to increased transcription of melanogenic enzymes (e.g., tyrosinase, TRP-1, TRP-2) and enhanced production of eumelanin. This photoprotective melanin absorbs and scatters ultraviolet (UV) and visible light, reducing oxidative DNA damage and phototoxicity. Unlike native α-MSH, afamelanotide has a prolonged half-life due to resistance to enzymatic degradation. **Key Research Findings** Afamelanotide is approved (as Scenesse) for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a disorder characterized by painful photosensitivity due to protoporphyrin IX accumulation. Phase III clinical trials demonstrated that subcutaneous afamelanotide implants significantly increased pain-free sun exposure time (from ~30 minutes to >2 hours) and improved quality of life, with reduced phototoxic reactions. Long-term safety data show no increased risk of melanoma or non-melanoma skin cancer, though transient nausea, flushing, and injection-site reactions are common. Studies also indicate potential off-label benefits in other photosensitivity disorders (e.g., solar urticaria, polymorphous light eruption) and UV-induced skin damage. **Clinical Relevance** Afamelanotide is the only approved therapy for EPP phototoxicity, offering a systemic approach to photoprotection that complements behavioral and physical sun avoidance. Its MC1R selectivity minimizes off-target melanocortin effects (e.g., on appetite or sexual function). Ongoing research explores its utility in actinic keratosis, vitiligo repigmentation, and as an adjuvant in photodynamic therapy. The drug is administered as a subcutaneous implant every two months, with efficacy dependent on consistent eumelanin induction. For research purposes only — not medical advice.
Key data
C78H111N21O19Research & studies
Vitiligo is a multifactorial disease with high quality-of-life impact.; No fully effective treatment currently exists for vitiligo.; Reviewed treatments include phototherapy, JAK inhibitors, TNF inhibitors, and others.; Long-term effectiveness and safety data for existing treatments are needed.
Setmelanotide was FDA-approved in 2020 for certain forms of syndromic obesity by engaging central melanocortin circuitry.; FDA approvals of bremelanotide and afamelanotide in 2019 demonstrate the safety of melanocortin receptor-targeting peptides.; The melanocortin system is a promising target for obesity, cachexia, and anorexia nervosa.; Potential applications include treating metabolic and behavioral disorders with pharmacological agents targeting melanocortin receptors.
Vitiligo involves progressive melanocyte loss due to multiple factors including metabolic abnormalities, oxidative stress, inflammation, and autoimmunity.; A convergence theory integrates these mechanisms into a comprehensive model of melanocyte viability reduction.; Afamelanotide, a melanocortin-1 receptor agonist, is used for erythropoietic protoporphyria and has not been linked to liver injury.; Advances in understanding pathogenesis have led to more targeted therapies with higher efficacy and fewer side effects.
Frequently asked questions
What is Melanotan I (Afamelanotide)?
**Mechanism of Action** Melanotan I (afamelanotide) is a synthetic tridecapeptide analog of α-melanocyte-stimulating hormone (α-MSH) that acts as a selective agonist at the melanocortin-1 receptor (MC1R). Activation of MC1R on melanocytes stimulates the cAMP-dependent signaling pathway, leading to increased transcripti
How does Melanotan I (Afamelanotide) work?
Selective MC1R agonist approved (Scenesse) to prevent phototoxicity in erythropoietic protoporphyria by stimulating eumelanin.
What is the research status of Melanotan I (Afamelanotide)?
Melanotan I (Afamelanotide) is currently classified as approved, with 104 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Melanotan I (Afamelanotide)?
Melanotan I (Afamelanotide) has a molecular weight of approximately 1646.8 g/mol (formula C78H111N21O19).
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