MK-0557 is a highly selective, orally available neuropeptide Y5 receptor antagonist with a Ki of 1.6 nM.
MK-0557 antagonizes the effects of the NPY5R-selective agonist on body-weight gain and hyperphagia in C57BL/6J mice and significantly suppresses the body-weight gain in diet-induced obese (DIO) mice. When lean mice on regular chow are switched to a medium high-fat diet (4.2 kcal/g) and treated with MK-0557 at 30 mg/kg PO QD, MK-0557 causes a 40% reduction inbody-weight gain at day 35[2].
MK-0557 antagonizes the effects of the NPY5R-selective agonist on body-weight gain and hyperphagia in C57BL/6J mice and significantly suppresses the body-weight gain in diet-induced obese (DIO) mice. When lean mice on regular chow are switched to a medium high-fat diet
[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. [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.