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1782235-14-6

中文名稱 1782235-14-6
英文名稱 CHIR 99021 trihydrochloride
CAS 1782235-14-6
分子式 C22H19Cl3N8
分子量 501.8
MOL 文件 1782235-14-6.mol
更新日期 2024/11/15 18:20:31
1782235-14-6 結(jié)構(gòu)式 1782235-14-6 結(jié)構(gòu)式

基本信息

中文別名
GSK-3Α/Β抑制劑(CHIR-99021 TRIHYDROCHLORIDE)
英文別名
CHIR-99021 3HCl
CT-99021 trihydrochloride)
CHIR 99021 trihydrochloride
CHIR-99021 trihydrochloride (CT99021 trihydrochloride
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

物理化學(xué)性質(zhì)

儲(chǔ)存條件-20°C儲(chǔ)存
溶解度DMSO:30.37(Max Conc. mg/mL);52.84(Max Conc. mM)
Water:16.69(Max Conc. mg/mL);29.04(Max Conc. mM)
形態(tài)Solid
顏色White to light yellow

常見問題列表

生物活性
CHIR-99021 trihydrochloride (CT99021 trihydrochloride) 是一種有效的選擇性 GSK-3α/β 抑制劑,IC50 為 10 nM 和 6.7 nM。CHIR-99021 trihydrochloride 對(duì) GSK-3 的選擇性比 CDC2,ERK2 和其他蛋白激酶高 500 倍以上。CHIR-99021 trihydrochloride 還是一種有效的 Wnt/β-catenin 信號(hào)通路激活劑。CHIR-99021 trihydrochloride 可增強(qiáng)小鼠和人類胚胎干細(xì)胞的自我更新。CHIR-99021 trihydrochloride 能誘導(dǎo)細(xì)胞自噬 (autophagy)。
靶點(diǎn)

GSK-3β

6.7 nM (IC 50 )

GSK-3α

10 nM (IC 50 )

cdc2

8800 nM (IC 50 )

體外研究

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.

體內(nèi)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.

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