GSK-923295 是一种特异性的变构着丝粒相关蛋白-E

GSK-923295 

GSK-923295 是一种特异性的变构着丝粒相关蛋白-E (CENP-E) 驱动蛋白 ATPase 活性抑制剂，作用于人类和犬类此酶，K_i 分别为 3.2±0.2 nM 和 1.6±0.1 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。

生物活性    
GSK-923295 is a special, allosteric inhibitor of centromere-associated protein-E (CENP-E) kinesin motor ATPase activity, with Ki of 3.2±0.2 nM and 1.6± 0.1 nM for human and canine, respectively.

IC50 & Target    
CENP-E
1.6 nM (Ki, Canine CENP-E)

体外研究
(In Vitro)    
GSK-923295 (GSK923295) is a first-in-class, specific, allosteric inhibitor of CENP-E kinesin motor function. GSK923295 is uncompetitive with both ATP and MT, inhibiting CENP-E MT-stimulated ATPase activity with a Ki of 3.2±0.2 nM and 1.6±0.1 nM for human and canine, respectively. GSK923295 inhibits release of inorganic phosphate and stabilized CENP-E motor domain interaction with microtubules[1]. GSK923295 has broad growth inhibitory activity in a panel of 237 cancer cell lines and produces significant tumor growth-delay in 8 of the 11 mouse xenograft tumor models with IC50s of 17.2 nM, 55.6 nM, 42 nM, and 51.9 nM for SW48, RKO (BRAF mutant), SW620 (KRAS mutant), and HCT116 (KRAS mutant), respectively[2]. GSK923295 is a potent and selective small molecule inhibitor of human CENPE with a Ki of 3.2 nM. GSK923295 demonstrates broad efficacy against a panel of 19 human neuroblastoma derived cell lines with an average growth IC50 of 41 nM[3].

体内研究
(In Vivo)    
Xenografts of mice treated with GSK-923295 (GSK923295) shows significant tumor growth delay compared to the control arm (NB-EBc1 p<0.0001; NB-1643 p=0.018; NB-1691 p=0.0018)[3].

分子量    
592.13

性状    
Solid

Formula    
C32H38ClN5O4

CAS 号    
1088965-37-0

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 30 mg/mL (50.66 mM; Need ultrasonic)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    1.6888 mL    8.4441 mL    16.8882 mL
5 mM    0.3378 mL    1.6888 mL    3.3776 mL
10 mM    0.1689 mL    0.8444 mL    1.6888 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 3 mg/mL (5.07 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: 3 mg/mL (5.07 mM); Suspended solution; Need ultrasonic

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 3 mg/mL (5.07 mM); Clear solution


 

参考文献

[1]. Wood KW, et al. 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.  [Content Brief] [2]. Mayes PA, et al. Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E (CENP-E) inhibition. Int J Cancer. 2013 Feb 1;132(3):E149-57.  [Content Brief] [3]. Balamuth NJ, et al. Serial transcriptome analysis and cross-species integration identifies centromere-associated protein E as a novel neuroblastoma target. Cancer Res. 2010 Apr 1;70(7):2749-58.  [Content Brief]