Melanocortin receptor family (MC1R-MC5R) (MCRs)

The melanocortin receptor (MCR) family consists of five G protein-coupled receptors (MC1R to MC5R) that mediate the physiological effects of melanocortin peptides, such as alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone [PMID: 14654744]. These receptors are distributed throughout the body and govern diverse functions: MC1R is primarily responsible for skin and hair pigmentation; MC2R regulates cortisol production in the adrenal cortex; MC3R and MC4R are critical for maintaining energy homeostasis and regulating appetite within the central nervous system; and MC5R is involved in exocrine gland function [PMID: 21849448]. Therapeutically, the MCR family is a major focus for treating metabolic and endocrine disorders. For example, setmelanotide is an MC4R agonist used for chronic weight management in patients with specific genetic obesity syndromes, while afamelanotide targets MC1R to increase melanin production for photoprotection [PMID: 33245855, PMID: 26133342]. Bremelanotide, another agonist, is approved for treating hypoactive sexual desire disorder in women [PMID: 31515757]. Despite their therapeutic potential, the structural similarity between MCR subtypes can lead to off-target effects, such as unwanted skin darkening or cardiovascular stimulation, necessitating the development of highly selective ligands.

Other names

Melanocortin receptorsMCRsMC-RMelanocortin receptor familyMC1RMC2RMC3RMC4RMC5R

Agonism of specific G protein-coupled receptor subtypes (MC1R-MC5R) leading to the activation of the Gs-adenylyl cyclase pathway and a subsequent increase in intracellular cyclic adenosine monophosphate (cAMP) levels [PMID: 14654744, PMID: 21849448].