MC4R
Hypothalamic G-protein-coupled receptor for α-MSH; regulates appetite, energy balance, and sexual function.
For laboratory and research use only — not for human consumption.
The melanocortin-4 receptor (MC4R) is a 332-amino-acid class A G-protein-coupled receptor expressed prominently in hypothalamic paraventricular and arcuate neurons, where it integrates signals from leptin, insulin, and the agouti-related peptide (AgRP) system to regulate appetite, energy expenditure, and autonomic tone. Endogenous α-melanocyte-stimulating hormone (α-MSH, derived from POMC processing) is the principal MC4R agonist; AgRP is its endogenous inverse agonist. Loss-of-function MC4R mutations are the most common monogenic cause of severe early-onset human obesity, identified in approximately 1–6% of severely obese cohorts. MC4R activation is exploited pharmacologically in two distinct directions: setmelanotide (Imcivree) is an MC4R agonist licensed for rare genetic obesity syndromes (POMC deficiency, leptin-receptor deficiency, Bardet-Biedl), and bremelanotide (PT-141) is a non-selective melanocortin-receptor agonist used for hypoactive sexual desire disorder where MC4R activation in central neural pathways drives sexual arousal. KPV (the C-terminal Lys-Pro-Val tripeptide of α-MSH) retains some melanocortin-pathway activity though its principal mechanism is intracellular NF-κB modulation rather than MC4R agonism.