基本信息

技术规格

安全信息

图形或危害标志
信号词	危险
危险性说明	H301 + H311 + H331 : 吞咽、皮肤接触或吸入中毒。 H315 : 造成皮肤刺激。 H319 : 造成严重眼刺激。
防范说明	P501 : 将内装物/容器送到批准的废物处理厂处理。 P261 : 避免吸入粉尘/烟/气体/烟雾/蒸气/喷雾。 P270 : 使用本产品时不要进食、饮水或吸烟。 P271 : 只能在室外或通风良好之处使用。 P264 : 作业后彻底清洗皮肤。 P280 : 戴防护手套/穿防护服/戴防护眼罩/戴防护面具。 P337 + P313 : 如仍觉眼刺激：求医/就诊。 P305 + P351 + P338 : 如进入眼睛：用水小心冲洗几分钟。如戴隐形眼镜并可方便地取出，取出隐形眼镜。继续冲洗。 P361 + P364 : 立即脱掉所有沾染的衣服，清洗后方可重新使用。 P332 + P313 : 如发生皮肤刺激：求医/就诊。 P301 + P310 + P330 : 如误吞咽：立即呼叫急救中心/医生。漱口。 P302 + P352 + P312 : 如皮肤沾染：用水充分清洗。如感觉不适，呼叫急救中心/医生。 P304 + P340 + P311 : 如误吸入：将人转移到空气新鲜处，保持呼吸舒适体位。呼叫急救中心/医生。 P403 + P233 : 存放在通风良好的地方。保持容器密闭。 P405 : 存放处须加锁。

运输信息

基本信息

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

基本信息

分子式
C22 H18 Cl2 N8

分子量
465.34

产品说明

一般描述

A cell-permeable aminopyrimidine compound that acts as potent, ATP-competitive, and highly selective GSK-3 inhibitor (IC₅₀ = 10 and 6.7 nM against GSK-3α and GSK-3β, respectively). Exhibits little or no activity toward 46 other enzymes (IC₅₀ >8.8 µM against 20 kinases and K_i ≥5 µM against 23 non-kinase enzymes) and shows only weak binding to 22 pharmacologically relevant receptors (K_d ~4 µM). This compound is orally available and is shown to effectively improve glucose metabolism in both murine and rat type 2 diabetes models in vivo. The solid form of this compound (Cat. No. 361559) is also available.

包装

5 mg in Glass bottle
Packaged under inert gas

生化/生理作用

Cell permeable: yes
Primary Target
GSK-3 α and β
Reversible: yes
Target IC₅₀: 10 and 6.7 nM against GSK-3&alpha

警告

Toxicity: Irritant (B)

外形

A 25 mM (5 mg/430 µL) solution of GSK-3 Inhibitor XVI, CHIR99021 (Cat. No. 361559) in DMSO.

其他说明

Mussmann, R., et al. 2007. J. Biol. Chem.282, 12030.
Ring, D.B., et al. 2003. Diabetes52, 588.
Bennett, C.N., et al. 2002. J. Biol. Chem.277, 30998.
Cline, G.W., et al. 2002.
Diabetes51, 2903.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

产品性质

安全信息

产品说明

一般描述

A cell-permeable aminopyrimidine compound that acts as potent, ATP-competitive, and highly selective GSK-3 inhibitor (IC₅₀ = 10 and 6.7 nM against GSK-3α and GSK-3β, respectively). CHIR99021 exhibits little or no activity toward 46 other enzymes (IC₅₀ >8.8 µM against 20 kinases and K_i ≥5 µM against 23 non-kinase enzymes) and shows only weak binding to 22 pharmacologically relevant receptors (K_d ~4 µM). CHIR99021 is orally available and is shown to effectively improve glucose metabolism in both murine and rat type 2 diabetes models in vivo.
A cell-permeable aminopyrimidine compound that acts as potent, ATP-competitive, and highly selective GSK-3 inhibitor (IC₅₀ = 10 and 6.7 nM against GSK-3α and GSK-3β, respectively). Exhibits little or no activity toward 46 other enzymes (IC₅₀ >8.8 µM against 20 kinases and K_i ≥5 µM against 23 non-kinase enzymes) and shows only weak binding to 22 pharmacologically relevant receptors (K_d ~4 µM). This compound is orally available and is shown to effectively improve glucose metabolism in both murine and rat type 2 diabetes models in vivo. Also available as a 25 mM solution in DMSO (Cat. No. 361571).

包装

5 mg in Plastic ampoule
Packaged under inert gas

警告

Toxicity: Harmful (C)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

其他说明

Mussmann, R., et al. 2007. J. Biol. Chem.282, 12030.
Ring, D.B., et al. 2003. Diabetes52, 588.
Bennett, C.N., et al. 2002. J. Biol. Chem.277, 30998.
Cline, G.W., et al. 2002. Diabetes51, 2903.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

产品性质

安全信息

产品说明

一般描述

CHIR99021是一种氨基嘧啶衍生物。CHIR99021通过抑制糖原合成酶激酶-3(GSK-3)活性而促进小鼠胚胎干细胞(ESCs)的自我更新潜能，并加强β-连环蛋白和c-Myc功能的上调。CHIR99021通过调节转化生长因子 β(TGF-β)、Notch和丝裂原活化蛋白激酶(MAPK)信号通路而促进胚胎干细胞的自我更新。CHIR99021是wnt(wingless/integrated)信号传导的激动剂，其在非小细胞肺癌(NSCLC)细胞中上调cyclinA表达并促进细胞增殖。

应用

CHIR99021已被用于：

• 与小分子混合，将人肺成纤维细胞转化为神经元
• 作为钾补充单纯形优化培养基(KSOM)的补充剂，用于胚泡培养
• 用于长期抑制GSK-3，以研究其在脑皮质发育中的作用

包装

5, 25 mg in glass bottle

生化/生理作用

CHIR99021是一种非常有效的糖原合酶激酶3(GSK3，对GSK3α和GSK3β的IC₅₀ 值分别为10和6.7 nM)抑制剂。 对CDK无交叉反应性。CHIR99201可增强人和小鼠胚胎干细胞的自我更新，并促进体细胞重编程为干细胞。

基本信息

产品性质

安全信息