化学信息：
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化学名
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6-[2-[[4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2-yl]amino]ethylamino]pyridine-3-carbonitrile
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简称
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CHIR-99021
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别名
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Chir 99021, Chir-99021, Chir99021, CT 99021, CT-99021, CT99021
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中文名
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N/A
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化学式
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C22H18Cl2N8
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分子量
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465.34
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CAS号
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252917-06-9
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纯度
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98%
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溶剂/溶解度
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Water<1mg/ml; DMSO78mg/ml; Ethanol<1mg/ml
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溶液配制
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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。
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生物信息：
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产品描述
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CHIR-99021 (CT99021)是一种GSK-3α和GSK-3β抑制剂，IC50分别为10nM和6.7nM。
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信号通路
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PI3K/Akt/mTOR; Stem Cells & Wnt
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靶点
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GSK-3β
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GSK-3α
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－
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－
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－
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IC50
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6.7nM
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10nM
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－
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－
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－
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体外研究
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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.
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体内研究
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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.
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临床实验
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N/A
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特征
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N/A
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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)：
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酶活性检测实验
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方法
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N/A
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细胞实验
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细胞系
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Insulin receptor-expressing CHO-IR cells; Primary rat hepatocytes
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浓度
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0.01-10μM
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处理时间
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30 min
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方法
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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.
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动物实验
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动物模型
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Female db/db mice; Male ZDF rats
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配制
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HCl salts formulated
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剂量
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8-48mg/kg
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给药方式
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oral administration
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参考文献：
1. Ring DB, et al. Diabetes. 2003, 52(3), 588-595.
包装清单：
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产品编号
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产品名称
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包装
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SF2708-10mM
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CHIR-99021 (GSK-3抑制剂)
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10mM×0.2ml
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SF2708-5mg
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CHIR-99021 (GSK-3抑制剂)
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5mg
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SF2708-25mg
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CHIR-99021 (GSK-3抑制剂)
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25mg
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—
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说明书
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1份
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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。
注意事项：
本产品对人体有毒，操作时请特别小心，并注意有效防护以避免直接接触人体或吸入体内。
本产品仅限于专业人员的科学研究用，不得用于临床诊断或治疗，不得用于食品或药品，不得存放于普通住宅内。
为了您的安全和健康，请穿实验服并戴一次性手套操作。
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