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) and enhanced production of photoprotective eumelanin. This results in a dose-dependent darkening of the skin independent of UV exposure, providing a physical barrier against ultraviolet radiation and visible light-induced oxidative stress. **Key Research Findings** Afamelanotide is approved (as Scenesse) for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a rare genetic disorder causing painful photosensitivity due to protoporphyrin IX accumulation. Phase III clinical trials demonstrated that subcutaneous administration of Afamelanotide (16 mg every 60 days) significantly increased pain-free sun exposure time and reduced the frequency and severity of phototoxic reactions compared to placebo. Long-term follow-up studies confirmed sustained efficacy and a favorable safety profile, with common adverse effects including nausea, flushing, and transient hyperpigmentation. **Clinical Relevance** Afamelanotide is the first and only approved pharmacotherapy for EPP, addressing an unmet need by reducing phototoxic episodes and improving quality of life. Its MC1R-selective mechanism avoids off-target melanocortin receptor activation (e.g., MC4R), minimizing appetite or sexual side effects seen with non-selective analogs. Off-label use for other photosensitivity disorders (e.g., solar urticaria, polymorphous light eruption) is under investigation, though regulatory approval remains limited to EPP. For research purposes only — not medical advice.
Key data
C78H111N21O19Research & studies
Vitiligo is caused by progressive melanocyte destruction involving oxidative stress, inflammation, genetics, and autoimmunity.; Recent advances in understanding etiopathogenesis have led to more effective treatments.; Janus kinase inhibitors, prostaglandin analogues, and antioxidants are among the promising new therapies.; Targeted phototherapy and excimer lasers offer additional therapeutic possibilities.
Afamelanotide is a synthetic alpha melanocyte stimulating hormone with higher activity than natural hormones.; It enhances eumelanin production by agonistically binding to the melanocortin-1 receptor.; Since 2016, it has been applied to treat erythropoietic protoporphyria (EPP), reducing painful photosensitivity.; Subcutaneous administration improved tolerance to artificial white light and increased pain-free time in direct sunlight.
Vitiligo has a multifactorial pathogenesis 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, anorexia nervosa, and other disorders.; Progress and challenges in developing melanocortin receptor-based therapeutics are reviewed.
Vitiligo is caused by 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 reduced melanocyte viability.; Afamelanotide, a melanocortin-1 receptor agonist, is used for light sensitivity in protoporphyrias and has no reported liver toxicity.; Improved understanding of pathogenesis has led to more targeted therapies with higher efficacy and fewer side effects.
Afamelanotide is an α-melanocyte-stimulating hormone analog that activates eumelanogenesis without UV exposure.; Clinical studies demonstrated significant increases in sunlight exposure and quality of life with afamelanotide treatment.; Common adverse events include headache, fatigue, and nausea.; The 60-day interval between implants may be insufficient for some patients based on effectiveness.
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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