Description
MK-0557 is a potent antagonist of the neuropeptide Y (NPY) receptor Y
5 (K
is = 1.3, 0.79, 0.74, and 1.4 nM for human, rhesus monkey, mouse, and rat receptors, respectively). It is >7,500-fold selective for Y
5 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 Y
5 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.
References
[1] Fichtner M, et al. Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2738-43. DOI:
10.1016/j.bmcl.2012.02.098[2] Erondu N, et al. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab. 2006 Oct;4(4):275-82. DOI:
10.1016/j.cmet.2006.08.002
