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GSK-923295

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Chemical Structure| 1088965-37-0 同义名 : GSK923295A
CAS号 : 1088965-37-0
货号 : A231503
分子式 : C32H38ClN5O4
纯度 : 99%+
分子量 : 592.128
MDL号 : MFCD16038931
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(50.66 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Kinesin

    CENP-E, Ki:3.2 nM
描述 Centromere-associated protein-E (CENP-E) is a kinetochore-associated mitotic kinesin that acts as a kinetochore microtubule receptor responsible for silencing mitotic checkpoint signal transduction. GSK923295 is a small allosteric inhibitor of CENP-E kinesin motor ATPase activity with a Ki value of 3.2 nM. GSK923295 at 20 μM resulted in quantitative recovery of CENP-E motor domain with the microtubule pellet, and dramatically slowed down the release rate of inorganic phosphate (Pi) from CENP-E. Continuous exposure of GSK923295 for 72h showed growth inhibitory activity (GI50 value) ranging from 12 nM to more than 10000 nM with an average GI50 of 253 nM and a median GI50 of 32 nM in 237 tumor cell lines[3]. In mice bearing colon tumor xenografts, 24h after a single injection of 125 mg/kg GSK923295 increased the appearance of mitotic figures and scattered apoptotic bodies in tumors. Compared to vehicle-treated mice, GSK923295 administration (31.1 – 125 mg/kg) also dose-dependently increased the ratio of 4n to 2n nuclei in dispersed tumor tissues of colon tumor xenografts. Among five xenografts that received two-week consecutive treatment of GSK923295 (125 mg/kg, three daily doses), one showed a complete tumor regression and four showed had partial tumor regressions[3].
作用机制 GSK923295 is an organic allosteric inhibitor of CENP-E microtubule-stimulated ATPase activity that inhibits the release of inorganic phosphate (Pi) and stabilizes CENP-E motor domain interaction with microtubules[3].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00504790 Cancer Phase 1 Completed - United States, California ... 展开 >> GSK Investigational Site Duarte, California, United States, 91010 United States, Michigan GSK Investigational Site Detroit, Michigan, United States, 48201 United States, Wisconsin GSK Investigational Site Madison, Wisconsin, United States, 53792-5666 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.69mL

0.34mL

0.17mL

8.44mL

1.69mL

0.84mL

16.89mL

3.38mL

1.69mL
参考文献

[1]Mayes PA, Degenhardt YY, et al. Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E inhibition. Int J Cancer. 2013 Feb 1;132(3):E149-57.

[2]Qian X, McDonald A, et al. Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295. ACS Med Chem Lett. 2010 Jan 19;1(1):30-4.

[3]Wood KW, Lad L, Luo L, Qian X, Knight SD, Nevins N, Brejc K, Sutton D, Gilmartin AG, Chua PR, Desai R, Schauer SP, McNulty DE, Annan RS, Belmont LD, Garcia C, Lee Y, Diamond MA, Faucette LF, Giardiniere M, Zhang S, Sun CM, Vidal JD, Lichtsteiner S, Cornwell WD, Greshock JD, Wooster RF, Finer JT, Copeland RA, Huang PS, Morgans DJ Jr, Dhanak D, Bergnes G, Sakowicz R, Jackson JR. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44.