化学信息：
| 化学名 | 6-[2-[[4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2-yl]amino]ethylamino]pyridine-3-carbonitrile |
|
| 简称 | CHIR-99021 | |
| 别名 |
Chir 99021, Chir-99021, Chir99021, CT 99021, CT-99021, CT99021 |
|
| 中文名 | N/A | |
| 化学式 | C22H18Cl2N8 | |
| 分子量 | 465.34 | |
| CAS号 | 252917-06-9 | |
| 纯度 | 98% | |
| 溶剂/溶解度 |
Water<1mg/ml; DMSO78mg/ml; Ethanol<1mg/ml |
|
| 溶液配制 | 5mg加入1.07ml DMSO，或者每4.65mg加入1ml DMSO，配制成10mM溶液。SF2708-10mM用DMSO配制。 |
生物信息：
| 产品描述 | CHIR-99021 (CT99021)是一种GSK-3α和GSK-3β抑制剂，IC50分别为10nM和6.7nM。 | ||||
| 信号通路 | PI3K/Akt/mTOR; Stem Cells & Wnt | ||||
| 靶点 | GSK-3β | GSK-3α | － | － | － |
| IC50 | 6.7nM | 10nM | － | － | － |
| 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 0.763μM. | ||||
| 体内研究 | Oral administration of CHIR-99021 at 30mg/kg enhances glucose metabolism in a rodent model of type 2 diabetes, with a maximal plasma glucose reduction of nearly 150mg/dl 3-4 hours after administration, while plasma insulin remains at or below control levels. Oral administration of CHIR-99021 at 16 or 48mg/kg 1 hour before oral glucose challenges in ZDF rats significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16mg/kg and 48mg/kg, respectively, and the higher dose of CHIR-99021 also reduces hyperglycemia before the oral glucose challenge. | ||||
| 临床实验 | N/A | ||||
| 特征 | N/A | ||||
相关实验数据(此数据来自于公开文献，碧云天并不保证其有效性)：
| 酶活性检测实验 | |
| 方法 | N/A |
| 细胞实验 | |
| 细胞系 | Insulin receptor-expressing CHO-IR cells; Primary rat hepatocytes |
| 浓度 | 0.01-10μM |
| 处理时间 | 30 min |
| 方法 | 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 2ml of medium without fetal bovine serum. After 24h, 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℃. Cells are lysed and centrifuged 15 min at 4℃/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 5mMol/l glucose-6-phosphate, using the filter paper assay of Thomas et al. |
| 动物实验 | |
| 动物模型 | Female db/db mice; Male ZDF rats |
| 配制 | HCl salts formulated |
| 剂量 | 8-48mg/kg |
| 给药方式 | oral administration |
| 产品编号 | 产品名称 | 包装 |
| SF2708-10mM | CHIR-99021 (GSK-3抑制剂) | 10mM×0.2ml |
| SF2708-5mg | CHIR-99021 (GSK-3抑制剂) | 5mg |
| SF2708-25mg | CHIR-99021 (GSK-3抑制剂) | 25mg |
| — | 说明书 | 1份 |
保存条件：
-20℃保存，至少一年有效。5mg和25mg包装也可室温保存，至少6个月有效。如果溶于非DMSO溶剂，建议分装后-80℃保存，预计6个月内有效。
