Setmelanotide Acetate CAS# 1504602-49-6

Setmelanotide acetate (RM-493) is a potent, selective melanocortin-4 receptor (MC4R) agonist developed for rare genetic obesity disorders. In preclinical assays, it activated human MC4R with an EC50 of ~0.27 nM and showed >20-fold selectivity over MC1R, MC3R, and MC5R. In diet-induced obese mice and genetic obesity models (e.g., Lep^ob/ob^ and MC4R-deficient variants), setmelanotide reduced food intake, body weight, and adiposity while increasing energy expenditure. Chronic administration normalized metabolic parameters, including glucose and insulin levels. Pharmacokinetic studies showed good subcutaneous bioavailability and dose-dependent plasma exposure. These findings supported its development as a targeted therapy for MC4R pathway–related obesity.