NMS-P715 是一种选择性的，ATP 竞争性的 MPS1 抑制剂，IC50 值为 182 nM。
CAS：1202055-32-0
分子式：C35H39F3N8O3
分子量：676.73
纯度：98%
存储：Store at -20°C

Background:

NMS-P715 is a selective, ATP-competitive inhibitor of MPS1, with an IC50 of 182 nM. Mps1|182 nM (IC50)|CK2|5.7 μM (IC50)|MELK|6.01 μM (IC50)|NEK6|6.02 μM (IC50)

NMS-P715 is a selective inhibitor of MPS1, with an IC50 of 182 nM. NMS-P715 is highly specific for MPS1, with no other kinases inhibited below an IC50 value of 5 μM and only 3 kinases inhibited below 10 μM (CK2, MELK, and NEK6). NMS-P715 promotes massive spindle assembly checkpoint (SAC) override with an EC50 of 65 nM. NMS-P715 (1 μM) causes mitotic acceleration in U2OS cells overexpressing YFP-α-tubulin, induces aneuploidy and inhibits the proliferation of HCT116 cells. NMS-P715 (0.5, 1 μM) affects mitotic checkpoint complex (MCC) stability and cdc20 ubiquitylation[1]. NMS-P715 (1 μM) exhibits bypass of the spindle assembly checkpoint and apoptosis in pancreatic ductal adenocarcinoma (PDAC) cell lines. NMS-P715 (0-25 μM) also selectively inhibits growth of PDAC cells[2].

NMS-P715 (10 mg/kg) exhibits an oral bioavailability of 37% and good pharmacokinetic properties in nude mice bearing subcutaneous implanted human tumor cell xenografts. NMS-P715 (90 mg/kg, p.o.) is well tolerated and cuases no signs of body weight loss or other overt toxicities in an A2780 ovary carcinoma xenograft model. NMS-P715 (100 mg/kg, p.o.) inhibits the tumor growth by appr 43% in the A375 melanoma xenograft model[1].

[1]. Colombo R, et al. Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase. Cancer Res. 2010 Dec 15;70(24):10255-64. [2]. Slee RB, et al. Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the mitotic MPS1 kinase inhibitor NMS-P715. Mol Cancer Ther. 2014 Feb;13(2):307-315.