CAS NO: | 1262417-51-5 |
规格: | 98% |
分子量: | 395.42 |
包装 | 价格(元) |
2mg | 电议 |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
Background:
NMS-P118 is a potent, orally available, and highly selective PARP-1 Inhibitor for cancer therapy.
NMS-P118 is found to be less myelotoxic in vitro than olaparib (now marketed as Lynparza), a dual PARP-1/-2 inhibitor. NMS-P118 proves to be metabolically stable, it modestly inhibites two cytochrome P450 family members (CYP-2B6 IC50: 8.15 uM; CYP-2D6 IC50: 9.51 uM) out of eight isoforms tested. Its ability in hampering the proliferation of bone marrow cells is from 5 to >60 times lower then olaparib according to the species[1].
NMS-P118 is a potent (KD=0.009 uM) PARP-1 inhibitor, showing 150-fold selectivity over PARP-2 (KD=1.39 uM). NMS-P118 possesses excellent pharmacokinetic profile and nearly complete oral bioavailability both in mice and rats. It proved to be highly efficacious in vivo both as single agent in MDA-MB-436 human breast cancer tumors and in combination with temozolomide in CAPAN-1 human pancreatic tumors growing as xenografts in the mouse. The compound is well tolerated at highly efficacious doses and is endowed with an excellent ADME profile[1].
参考文献:
[1]. Papeo G, et al. Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. J Med Chem. 2015 Sep 10;58(17):6875-98.