MPI-0479605

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MPI-0479605 是一种 ATP 竞争性选择性抑制剂。

MPI-0479605 is a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild-type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.

MPI-0479605 is a potent and selective ATP-competitive inhibitor of Mps1, with an IC50 of 1.8 nM. MPI-0479605 (0.1-10 μM) reduces cell viability of HCT-116 cells in a dose-dependent manner. MPI-0479605 shows severe defects in the ability to align chromosomes at the metaphase plate, but causes complete cytokinesis.

MPI-0479605 (30 mg/kg daily or 150 mg/kg every fourth day (Q4D), i.p.) inhibits tumor growth by 49% and 74 % in HCT-116 xenografts. However, MPI-0479605 does not show inhibitory activity via daily dosing on the Colo-205 xenografts, and dosing every four days causes 63% tumor growth inhibition (TGI).

MPI0479605 | MPI 0479605 | MPI-0479605

Endocrinology/Hormones

CaMK

Mps1

Cancer

——

1246529-32-7

407.51

C22H29N7O

>98% (HPLC)

DMSO : 11 mg/mL. 26.99 mM;

n1c(nc(c2c1[nH]cn2)NC1CCCCC1)Nc1c(cc(cc1)N1CCOCC1)C

N6-cyclohexyl-N2-(2-methyl-4-morpholinophenyl)-9H-purine-2,6-diamine

(-20℃)

With Ice Pack

≥ 2 years