252917-06-9
252917-06-9 结构式
基本信息
6-[2-[4-(2,4-二氯苯基)-5-(4-甲基-1H-咪唑-2-基)嘧啶-2-基氨基]乙基氨基]吡啶-3-甲腈
6-[[2-[[4-(2,4-二氯苯基)-5-(5-甲基-1H-咪唑-2-基)-2-嘧啶]氨基]乙基]氨基]-3-吡啶甲腈
CHIR-99021
GSK-3 Inhibitor XVI
CT 99021(CHIR 99021)
CHIR 99021(CT 99021)
CHIR-99021 (CT99021) HCl
CHIR 911, GSK-3 Inhibitor XVI
CHIR-99021 GSK-3 Inhibitor XVI
6-[2-[4-(2,4-Dichlorophenyl)-5-(4-Methyl-1H-iMidazol-2-yl)pyriMidin-2-ylaMino]ethylaMino]pyridine-3-
6-{2-[4-(2,4-Dichloro-phenyl)-5-(4-methyl-1H-imidazol-2-yl)-pyrimidin-2-ylamino]-ethylamino}-nicotinonitrile
物理化学性质
安全数据
常见问题列表
| Target | Value |
|
GSK-3β
(Cell-free assay) | 6.7 nM |
|
GSK-3α
(Cell-free assay) | 10 nM |
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.
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.