GSK-923295

GSK-923295CAS号: 1088965-37-0分子式: C32H38ClN5O4分子量: 592.13描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)

产品描述
描述
GSK923295 is a first-in-class, specific allosteric inhibitor of CENP-E kinesin motor ATPase with Ki of 3.2 nM, and less potent to mutant I182 and T183. Phase 1.
纯度
>98%
储存/保存方法
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
基本信息
别名
GSK-923295,GSK923295
外观
Powder
可溶性/溶解性
DMSO 100 mg/mL (168.88 mM)

Ethanol 100 mg/mL (168.88 mM)

生物活性
靶点
CENP-E
In vitro(体外研究)
GSK923295 is the first potent and selective inhibitor of the mitotic kinesin centromere-associated protein-E (CENP-E). GSK923295 is uncompetitive with both ATP and microtubules (MT), inhibiting CENP-E MT-stimulated ATPase activity with a Ki of 3.2 nM, highly selective over other kinesins. GSK923295 inhibits release of inorganic phosphate and stabilizes CENP-E motor domain interaction with microtubules, reduces the rate of ATP-promoted dissociation of CENP-E from MT (koff, MT) by more than 50-fold. GSK923295 causes failure of metaphase chromosome alignment and induces mitotic arrest. GSK923295 is a potent inhibitor of tumor cell growth, with an average GI50 of 253 nM and a median GI50 of 32 nM for 237 tumor cell lines. GSK923295 inhibits tumor cell growth more effectively when mitogen-activated protein kinase (MEK/ERK) signaling is also inhibited.
In vivo(体内研究)
GSK923295 produces clear increases in the abundance of mitotic figures and scattered apoptotic bodies in tumors. GSK923295 causes a dose-dependent increase in the ratio of 4n to 2n nuclei. GSK923295 exhibits robust, dose-dependent antitumor activity against Colo205 xenografts, including partial and complete regressions at the 125 mg/kg dose. GSK923295 demonstrates significant antitumor activity against solid tumor models, inducing CRs in Ewing sarcoma, rhabdoid, and rhabdomyosarcoma xenografts, may be a valuable therapeutic target in pediatric cancer.

分子结构图

GSK-923295