MK-0557 is a potent antagonist of the neuropeptide Y (NPY) receptor Y5 (Kis = 1.3, 0.79, 0.74, and 1.4 nM for human, rhesus monkey, mouse, and rat receptors, respectively).1 It is >7,500-fold selective for Y5 over other receptors and lacks activity in a panel of 180 receptors, enzymes, and ion channels at concentrations up to 1 μM. MK-0557 increases intracellular calcium in CHO cells expressing the human Y5 receptor in a concentration-dependent manner. In vivo, MK-0557 (30 mg/kg) reduces body weight gain in wild-type and diet-induced obese mice. It also reduces retroperitoneal fat pad weight, epididymal and mesenteric fat pad weights, leptin levels, and food intake in lean mice fed a high-fat diet.
1.Erondu, N., Gantz, I., Musser, B., et al.Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adultsCell Metab.4(4)275-282(2006)