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 |
