Pharmacology & Mechanism of Action
SCENESSE® (afamelanotide 16mg) is a selective agonist of the MC1R (melanocortin 1 receptor). It has been developed with the aim of delivering medicinal photoprotection for therapeutic benefit. As an analogue of the naturally occurring melanocortin alpha-MSH, its mechanism of action is biomimicry (in part) of the natural human tanning response.
SCENESSE® delivers its photoprotective response through a ‘signaling cascade’ following from its selective binding and activation of the MC1 receptor in melanocytes.
When SCENESSE® binds with MC1R on the surface of melanocyte cells in the epidermis of the skin, it begins a series of actions and reactions that result in the melanocyte favouring the production of eumelanin (black/brown) over pheomelanin (red/yellow).
The initial binding stimulates the MC1R leading to the activation of adenylate cyclase (AC) and stimulation of production of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). cAMP in turn activates the protein kinase A (PKA) leading to the phosphorylation of the cAMP-responsive element (CREB). Phosphorylated CREB will bind to the cAMP-responsive element on the microphthalmia-associated transcription factor (MITF) gene leading to the MITF protein synthesis. MITF has the ability to activate several genes by binding on them; including the MC1R genes, and the genes involved in melanogenesis (tyrosinase, TRP1 and TRP2 genes).This results in heightened levels of the melanogenic enzymes (tyrosinase,TRP1 and TRP2) within the melanocyte. It is the level of these enzymes within a melanocyte that dictates whether the cell will create eumelanin (photoprotective black/brown pigment) rather than pheomelanin (red/yellow pigment).
Melanocytes creating eumelanin, thereby increasing pigmentation of the skin and thus providing photoprotection is the therapeutic benefit intended from the administration of afamelanotide.