1782235-14-6

中文名称:

1782235-14-6

中文同义词:

GSK-3Α/Β抑制剂(CHIR-99021 TRIHYDROCHLORIDE)

英文名称:

CHIR 99021 trihydrochloride

英文同义词:

CHIR 99021 trihydrochloride;CHIR-99021 3HCl;CT99021 TRIHYDROCHLORIDE;CHIR99021 TRIHYDROCHLORIDE;CHIR 99021 TRIHYDROCHLORIDE;CT-99021 TRIHYDROCHLORIDE;6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile trihydrochloride;CHIR-99021 trihydrochloride (CT99021 trihydrochloride;CT-99021 trihydrochloride)

CAS号:

1782235-14-6

分子式:

分子量:

0

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

Mol File

生物活性

CHIR-99021 trihydrochloride (CT99021 trihydrochloride) 是一种有效的选择性 GSK-3α/β 抑制剂，IC50 为 10 nM 和 6.7 nM。CHIR-99021 trihydrochloride 对 GSK-3 的选择性比 CDC2，ERK2 和其他蛋白激酶高 500 倍以上。CHIR-99021 trihydrochloride 还是一种有效的 Wnt/β-catenin 信号通路激活剂。CHIR-99021 trihydrochloride 可增强小鼠和人类胚胎干细胞的自我更新。CHIR-99021 trihydrochloride 能诱导细胞自噬 (autophagy)。

靶点

GSK-3β 6.7 nM (IC 50 ) GSK-3α 10 nM (IC 50 ) cdc2 8800 nM (IC 50 )

GSK-3β 6.7 nM (IC 50 )

GSK-3α 10 nM (IC 50 )

体外研究

CHIR-99021 inhibits human GSK-3β with K i values of 9.8 nM. CHIR-99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR-99021 specifically inhibits GSK3β (IC 50 =~5 nM) and GSK3α (IC 50 =~10 nM), with little effect on other kinases. In the presence of CHIR-99021 the viability of the ES-D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM CHIR-99021 with an IC 50 of 4.9 μM.

体内研究

In ZDF rats, a single oral dose of CHIR-99021 (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration. CHIR99021 (2 mg/kg) given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). CHIR99021 treatment significantly blocks crypt apoptosis and accumulation of p-H2AX + cells, and improves crypt regeneration and villus height. CHIR99021 treatment increases Lgr5 + cell survival by blocking apoptosis, and effectively prevents the reduction of Olfm4, Lgr5 and CD44 as early as 4 h.