Setmelanotide

Setmelanotide (RM-493) is a selective melanocortin 4 receptor (MC4R) agonist with EC₅₀s of 0.27 nM and 0.28 nM for human and rat MC4R, respectively^[1]. IC50 & Target:Ki:3.9 nM (hMC1R), 10 nM (hMC3R), 2.1 nM (hMC4R), 430 nM (hMC5R), 2.7 nM (rMC4R)^[1]
EC50: 5.8 nM (hMC1R), 5.3nM (hMC3R), 0.27 nM (hMC4R), 0.28 (rMC4R), 1600 nM (hMC5R)^[1] In Vitro: Melanocortin receptor agonists act in the brain to regulate food intake and body weight and, independently of these actions. Setmelanotide exhibits agonist activity to human and rat MC4R with K_is of 2.1 and 2.7 nM and EC₅₀s of 0.27 and 0.28 nM, respectively^[1]. In Vivo: Inhibition of refeeding after an overnight fast by Setmelanotide is dependent on functional MC4R, and does not require MC3R. BIM-22493 acutely improves glucose homeostasis. Lep^ob/Lep^ob mice treated with BIM-22493 exhibits significantly improved glucose clearance when compared to controls. Chronic BIM-22493 treatment was associated with significantly lower levels of serum glucose and HOMA-IR values^[1].
Treatment with setmelanotide results in transient decreases in food intake (35%), with persistent weight loss over 8 weeks of treatment (13.5%) in a diet-induced obese nonhuman primate model^[2].