For research use only. Not for therapeutic Use.
MK-0557 is a highly selective, orally available neuropeptide Y5 receptor antagonist with a Ki of 1.6 nM.
Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti-obesity drug target. MK-0557 has a Ki=1.3 nM at the human NPY5R, with similar affinities at rhesus, mouse, and rat NPY5R. MK-0557 has no significant binding to the human NPY1R, NPY2R, NPY4R, or mouse NPY6R at concentrations of 10 μM[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 (4.2 kcal/g) and treated with MK-0557 at 30 mg/kg PO QD, MK-0557 causes a 40% reduction in
body-weight gain at day 35[2].
| Catalog Number | I008012 |
| CAS Number | 328232-95-7 |
| Synonyms | N-[1-(2-fluorophenyl)pyrazol-3-yl]-1′-oxospiro[cyclohexane-4,3′-furo[3,4-c]pyridine]-1-carboxamide |
| Molecular Formula | C22H19FN4O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C22H19FN4O3/c23-17-3-1-2-4-18(17)27-12-8-19(26-27)25-20(28)14-5-9-22(10-6-14)16-13-24-11-7-15(16)21(29)30-22/h1-4,7-8,11-14H,5-6,9-10H2,(H,25,26,28) |
| InChIKey | RMYZIRFUCOMQRH-UHFFFAOYSA-N |
| SMILES | C1CC2(CCC1C(=O)NC3=NN(C=C3)C4=CC=CC=C4F)C5=C(C=CN=C5)C(=O)O2 |
| Reference | [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. |
