Afamelanotide

Chemical Identity

Property	Value
Chemical Formula	C78H111N21O19
Molecular Weight	1646.8 Da
CAS Number	75921-69-6
Peptide Class	Melanocortin Agonist (NDP-alpha-MSH)
Route	SC implant

Structure

Afamelanotide (Scenesse) is a synthetic analog of alpha-melanocyte-stimulating hormone (alpha-MSH) with substitutions of D-phenylalanine for L-phenylalanine at position 4, norleucine for methionine at position 7, and valine for histidine at position 10. These modifications increase MC1R binding affinity 10-1000 fold and resist enzymatic degradation.

Mechanism of Action

Afamelanotide binds melanocortin 1 receptor (MC1R) on melanocytes, activating adenylyl cyclase and increasing cAMP. This stimulates melanogenesis (eumelanin production), providing photoprotection against UV radiation. In erythropoietic protoporphyria (EPP), increased melanin reduces painful phototoxic reactions.

Clinical Applications

• Erythropoietic protoporphyria: Prevention of phototoxic reactions (Scenesse)
• Vitiligo: Repigmentation (investigational)
• Solar urticaria: Photoprotection
• Photodermatoses: UV protection in various conditions

Pharmacokinetics

• Half-life: 30 days (subcutaneous implant)
• Onset: Melanin increase within 2 days
• Duration: 60 days per implant
• Bioavailability: 100% (implant)
• Route: SC implant (upper arm)

Safety and Side Effects

Nausea, hyperpigmentation (including naevi), injection site reactions, headache, and nasopharyngitis. No serious adverse effects in clinical trials. Regular dermatological monitoring recommended.

References

• Langendonk, J.G., et al. (2015). Afamelanotide for EPP. New England Journal of Medicine, 373, 48-59.
• Fabrikant, J., et al. (2013). Afamelanotide and EPP. Photodermatology, Photoimmunology & Photomedicine, 29, 258-266.