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The Melanocortin system has been largely unexplored in drug development but recent approvals, its novelty and wide-spread application across indications has led it to the frontier of new discoveries in medicine. Since Vyleesi approval multiple companies have initiated drug discovery programs targeting the melanocortin system.
The central melanocortin system is defined anatomically as a collection of central nervous system circuits which include: Neurons that express hypothalamic neuropeptide Y and agouti gene-related protein or proopiomelanocortin (POMC) and that originate in the arcuate nucleus .
Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system [ 1 ] each with differing specificities for melanocortins : [ 2 ] [ 3 ] [ 4 ]
Proopiomelanocortin has been shown to interact with melanocortin 4 receptor. [21] [22] The endogenous agonists of melanocortin 4 receptor include α-MSH, β-MSH, γ-MSH, and ACTH. The fact that these are all cleavage products of POMC should suggest likely mechanisms of this interaction. [citation needed]
The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones known as the melanocortins, which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH).
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Melanocortin 4 receptor (MC 4 R) is a melanocortin receptor that in humans is encoded by the MC4R gene highly expressed in paraventricular nucleus of the hypothalamus. [ 5 ] [ 6 ] [ 7 ] It encodes the MC 4 R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH).