Setmelanotide (BIM-22493) is a selective agonist of melanocortin 4 receptor (MC4R)(human and rat MC4R with EC50s of 0.27 nM and 0.28 nM, respectively).

MC1R (human):3.9 nM (ki), MC1R (human):5.8 nM (EC50), MC4R (human): 0.27 nM (EC50), MC4R (rat): 2.7 nM (ki), MC5R (human): 1600 nM (EC50), MC5R (human): 430 nM (ki), MC3R (human): 5.3nM (EC50), MC4R (human): 2.1 nM (ki), MC4R (rat):0.28 Nm (EC50), MC3R (human): 10 nM (ki)

Melanocortin receptor agonists act in the brain to regulate food intake and body weight and, independently of these actions, affect insulin sensitivity. Setmelanotide exhibits agonist activity to human and rat MC4R(human and rat MC4R with Kis of 2.1 and 2.7 nM and EC50s of 0.27 and 0.28 nM, respectively)[1].

Inhibition of refeeding after an overnight fast by BIM-22493 is dependent on functional MC4R.glucose homeostasis acutely improved by BIM-22493. BIM-22493(Lepob/Lepob mice) exhibits significantly improved glucose clearance when compared to controls. Chronic BIM-22493 treatment was associated with significantly lower levels of serum insulin, glucose and HOMA-IR values, suggesting an improvement in insulin sensitivity[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].