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GSK-923295

现货
Catalog No.
A3450
CENP-E抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,100.00
Ship with 10-15 days
5mg
¥ 1,100.00
Ship with 10-15 days
10mg
¥ 1,800.00
Ship with 10-15 days
50mg
¥ 6,300.00
Ship with 10-15 days

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Background

GSK923295 is a specific inhibitor of CENP-E kinesin motor with IC50 value of 3.2 nM [1].

Centromere-associated protein E (CENP-E) is a mitotic kinesin, which is the connect of mitosis process with the mitotic checkpoint signaling. It Interacts with spindle microtubules and contribute to the chromosome alignment, and thus it regulates the cell-cycle transition from metaphase to anaphase.

When asynchronous cultured cells were exposed to GSK923295, the penetrant cell-cycle delay in mitosis was observed, which accompanied with morphological changes similar to RNAi-mediated knockdown of CENP-E mRNA. It indicated a significant inhibition of CENP-E by GSK923295. In the presence of GSK9232195, CENP-E microtubule (MT)-stimulated ATPase showed a dramatic slowing of release of ADP and Pi, where the ATP-bound form was stabilized and the activity of CENP-E was inhibited. This observation suggested GSK923295 inhibited CENP-E via the suppression of MT-stimulated ATPase [1].

In mouse model, mice bearing xenografts of the Colo205 colon tumor cell line were administered with GSK923295 of 125 mg/kg. The result showed GSK923295-induced cell-cycle changes of tumor cells and increased scattered apoptosis body. Additionally, long-term study via measuring tumor volume revealed significant antitumor activity of GSK923295, in a manner of dose-dependent [1].

Reference:
[1] Wood K W et al. , Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. 2010, 107 (13): 5839-5844.

文献引用

1. Amin MA, McKenney RJ, et al. "Antagonism between the dynein and Ndc80 complexes at kinetochores controls the stability of kinetochore-microtubule attachments during mitosis." J Biol Chem. 2018 Apr 20;293(16):5755-5765. PMID:29475948

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt592.14
Cas No.1088965-37-0
FormulaC32H38ClN5O4
SynonymsGSK 923295;GSK923295
Solubility≥29.6mg/mL in DMSO
Chemical Name3-chloro-N-[(2S)-1-[[2-(dimethylamino)acetyl]amino]-3-[4-[8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl]phenyl]propan-2-yl]-4-propan-2-yloxybenzamide
SDFDownload SDF
Canonical SMILESCC(C)OC1=C(C=C(C=C1)C(=O)NC(CC2=CC=C(C=C2)C3=CN4C=CC=C(C4=N3)C(C)O)CNC(=O)CN(C)C)Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

酶学研究

使用大肠杆菌BL21 (DE3) 表达驱动蛋白并将其纯化。CENP-E蛋白包括6-his标记的2 ~ 340残基羧基末端。在PEM25 Buffer [25 mM PipesK+ (pH 6.8), 2 mM MgCl2, 1 mM EGTA] (含10 μM Paclitaxel)中,使用MT开展实验。在PEM25 Buffer(500 μM ATP,5 μM MT和1 nM CENP-E)中,测定达稳态抑制时的IC50值。

细胞实验 [1]:

细胞系

肿瘤细胞系

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

~ 10 μM;72小时

实验结果

在237种肿瘤细胞系中,GSK923295有效抑制肿瘤细胞生长,GI50的平均值为253 nM,GI50值的中位数为32 nM。

动物实验 [1]:

动物模型

携带Colo205异种移植瘤的小鼠

给药剂量

125 mg/kg;腹腔注射;相隔1周每天注射3次,持续2个周期

实验结果

GSK923295有效抑制肿瘤,上述作用具有剂量依赖性。在125 mg的剂量下,GSK923295导致部分或完全的肿瘤消退。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Wood K W et al. , Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. 2010, 107 (13): 5839-5844.

生物活性

Description GSK-923295是有丝分裂驱动蛋白着丝粒相关蛋白E (CENP-E)的小分子抑制剂,Ki值为3.2 nM。
靶点 CENP-E          
IC50 3.2 nM (Ki)          

质量控制