CHIR-99021

产品名称：

252917-06-9
CHIR-99021
6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile

产品介绍：

基本信息

分子式	C₂₂H₁₈Cl₂N₈
分子量	465.34
熔点	316.33
沸点	784.08
密度	1.48
折光率(n20D)	1.7
存储条件	Freezer -20℃

产品描述

CHIR-99021 (CT99021)是一种GSK-3α和GSK-3β抑制剂， IC50分别为10 nM and 6.7 nM。CHIR99201对CDKs没有交叉反应性，对GSK-3β的选择性是对CDKs选择性的350倍。

靶点（IC50 & Targe）

GSK-3α,10 nM (cell free)

GSK-3β,6.7 nM (cell free)

体外研究

CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases. Furthermore, CHIR-99021 shows only weak binding to a panel of 22 pharmacologically relevant receptors and little inhibitory activity against a panel of 23 nonkinase enzymes. CHIR-99021 induces the activation of glycogen synthase (GS) in insulin receptor-expressing CHO-IR cells with EC50 of 0.763 μM[1].

体内研究

Oral administration of CHIR-99021 at 30 mg/kg enhances glucose metabolism in a rodent model of type 2 diabetes, with a maximal plasma glucose reduction of nearly 150 mg/dl 3-4 hours after administration, while plasma insulin remains at or below control levels. Oral administration of CHIR-99021 at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16 mg/kg and 48 mg/kg, respectively, and the higher dose of CHIR-99021 also reduces hyperglycemia before the oral glucose challenge[1].

细胞实验

Cell lines: Insulin receptor–expressing CHO-IR cells; Primary rat hepatocytes

Concentrations: 0.01-10 μM

Incubation Time: 30 min

Method:CHO-IR cells expressing human insulin receptor are grown to 80% confluence in Hamm’s F12 medium with 10% fetal bovine serum and without hypoxanthine. Trypsinized cells are seeded in 6-well plates at 1 × 106 cells/well in 2 ml of medium without fetal bovine serum. After 24 h, medium is replaced with 1 ml of serum-free medium containing GSK-3 inhibitor or control (final DMSO concentration <0.1%) for 30 min at 37°C. Cells are lysed and centrifuged 15 min at 4°C/14000g. The activity ratio of GS is calculated as the GS activity in the absence of glucose-6-phosphate divided by the activity in the presence of 5 mmol/l glucose-6-phosphate, using the filter paper assay of Thomas et al.

(Only for Reference)

动物实验

Animal Models: Female db/db mice; Male ZDF rats

Formulation: HCl salts formulated

Dosages: 8-48 mg/kg

Administration: oral administration

(Only for Reference)

参考文献

[1] Ring DB, et al. Diabetes. 2003, 52(3):588-595.

安全信息

图形或危害标志
提示语	Danger
危险说明	H300 H315 H319 H335
防范说明	P261 P264 P301+P310 P305+P351+P338
UN号码	2811
危险分类	6.1
包装等级	III