Melanocortin Receptor
A family of five G-protein coupled receptors (MC1R through MC5R) that regulate skin pigmentation, appetite, sexual function, inflammation, and adrenal steroid production. Afamelanotide targets MC1R, setmelanotide targets MC4R, and bremelanotide acts on MC3R/MC4R.
Technical Context
The five MCRs have distinct tissue distributions and functions: MC1R (melanocytes → pigmentation; afamelanotide is an agonist), MC2R (adrenal cortex → cortisol production via ACTH; corticotropin and cosyntropin act here), MC3R (brain → energy homeostasis; bremelanotide activates MC3R and MC4R), MC4R (hypothalamus → appetite and energy balance; setmelanotide is a selective MC4R agonist for genetic obesity), MC5R (sebaceous glands and other tissues → sebum production). The endogenous ligands are melanocortins derived from proopiomelanocortin (POMC): α-MSH, β-MSH, γ-MSH, and ACTH. Agouti-related peptide (AgRP) is an endogenous MC3R/MC4R antagonist. MC4R loss-of-function mutations cause monogenic obesity — the specific target of setmelanotide.