基本信息

技术规格

物性(参考值)

基本信息

产品描述

SB216763是一种有效的，选择性GSK-3α抑制剂，IC50为34.3 nM；对GSK-3β具有同样的抑制作用。

靶点（IC50 & Targe）

GSK-3α,34.3nM

GSK-3β,～34.3nM

体外研究

除了抑制GSK-3α,SB 216763也同样有效作用于 GSK-3β，按10 μM 处理，抑制达96%， 作用于24 种其他蛋白激酶包括 PKBα 和PDK1时具有最小活性，IC50>10 μM。SB-216763作用于人肝脏细胞，刺激糖原合成，EC50为3.6 μM, 且作用于HEK293 细胞，诱导β-catenin-LEF/TCF相关报告基因的转录，这种作用存在剂量依赖性，按 5 μM处理，诱导达到最大值，增大2.5倍。[1]与剂量依赖性显著抑制GSK-3 活性一致，SB 216763 保护小脑颗粒神经元免受 LY-294002或钾丧失而诱导的细胞凋亡，这种作用具有浓度依赖性，3 μM 时保护神经达到最高值，与10 mM LiCl作用效果形成对比。3 μM SB 216763完全抑制 LY-294002诱导的 鸡背根神经节感觉神经元死亡。5 μM SB 216763 作用于HEK293细胞，显著抑制小脑颗粒神经元中GSK-3依赖的神经元特异性微管相关蛋白的磷酸化，且提高β-catenin细胞质水平，与Wnt调节的 GSK-3抑制效果差不多。[2] 25-50 μM SB 216763作用于前列腺癌细胞系，包括BXPC-3, MIA-PaCa2, PANC1, ASPC1, 和CFPAC, 降低细胞活力，这种作用存在剂量依赖性，且显著促进凋亡，处理72小时,凋亡达50%,而对HMEC或WI38细胞系没有作用效果。[3]

体内研究

SB 216763 按20 mg/kg 剂量处理患Bleomycin (BLM)诱导肺部炎症和纤维化的小鼠，通过显著抑制炎症细胞因子MCP-1和TNF-α的产量，显著抑制肺部炎症和纤维化，且显著提高BLM处理小鼠的寿命。SB 216763 处理，通过抑制肺泡上皮细胞损伤，而显著降低 BLM诱导的肺泡。[4]

激酶实验

GSK-3 活性检测:

在不同浓度SB 216763存在时,在含1 nM 人GSK-3α, 50 mM MOPS pH 7.0,0.2 mM EDTA, 10 mM Mg(Ac)2,7.5 mM β-巯基乙醇,5% (w/v)甘油,0.01% (w/v) Tween-20, 10% (v/v) DMSO, 及28 μM GS-2 肽底物的反应混合物中，测量GSK-3激酶活性。GS-2肽序列对应GSK-3使糖原合酶磷酸的地区。加入0.34 μCi [33P]γ-ATP开始实验。全部ATP浓度为 10 μM。实验在室温下进行30分钟后，加入含21 mM ATP的1/3实验体积为2.5%(v/v) H3PO4，终止反应。样本在P30磷酸纤维垫上展开，然后在0.5% (v/v) H3PO4中冲洗6次。过滤垫密封到Wallac betaplate闪烁液的样品袋中。在 Wallac microbeta闪烁计数器中计算测定33P 渗透到底物肽中的量。

细胞实验

Cell lines: BXPC-3, MIA-PaCa2, PANC1, ASPC1, 和CFPAC

Concentrations: 溶于DMSO, 终浓度为～50 μM

Incubation Time: 24, 48, 和72小时

Method: 使用不同浓度SB 216763处理细胞 24,48和 72小时。通过MTS检测测量相对细胞活力。使用 Hoechst染色而测定凋亡细胞。

(Only for Reference)

动物实验

Animal Models: 患Bleomycin (BLM)诱导的肺部炎症和纤维化的C57BL/6N小鼠

Formulation: 溶于DMSO, 在盐水中稀释

Dosages: 20 mg/kg

Administration: 静脉注射

(Only for Reference)

参考文献

[1] Coghlan MP, et al. Chem Biol, 2000, 7(10), 793-803.

[2] Cross DA, et al. J Neurochem, 2001, 77(1), 94-102.

[3] Ougolkov AV, et al. Cancer Res, 2005, 65(6), 2076-2081.

[4] Gurrieri C, et al. J Pharmacol Exp Ther, 2010, 332(3), 785-794.

安全信息

图形或危害标志
提示语	Warning
危险说明	H315 H319 H335
防范说明	P261 P305+P351+P338
WGK	3

产品说明

应用

使用 SB-216763 抑制人脑微血管内皮细胞系 和大肠癌细胞中的 GSK-3β。

包装

5, 25 mg in glass bottle

生化/生理作用

SB-216763 是一种与 ATP 竞争并强效抑制 α和 βGSK-3 的同工酶。作为神经保护剂，它防止 PI3-激酶途径诱导的神经细胞死亡。它还可以延迟预处理，减少梗死面积，防止心肌缺血。
强效、选择性、细胞渗透性糖原合成酶激酶-3 (GSK-3) 抑制剂。

特点和优势

该化合物是激酶磷酸酶生物学研究的特色产品。 点击此处 ，发现更多特色激酶磷酸酶生物学产品。前往 sigma.com/discover-bsm 了解更多关于其他研究领域的生物活性小分子。
该化合物出现在《受体分类和信号转导手册》的 GSK-3 和 PKB/Akt 页。要浏览其他手册页， 单击此处 。
该化合物由 GlaxoSmithKline 开发。要浏览其他制药公司开发的化合物列表批准的药物/候选药物的列表， 点击这里 。

法律信息

根据GlaxoSmithKline的协议出售用于研究目的

基本信息

产品性质

安全信息

产品说明

一般描述

A cell-permeable (aryl,indole) maleimide compound that acts as a potent, selective, ATP-competitive inhibitor of GSK-3 activity (K_i = 9.1 nM for GSK-3α). At 10 µM concentration, does not significantly inhibit a panel of 24 other protein kinases tested. Reported to stimulate glycogen synthesis in Chang human liver cells (EC₅₀ = 3.6 µM) and induce transcription of β-catenin-LEF/TCF (lymphoid enhancer factor/T cell factor) regulated reporter gene in HEK293 human embryonic kidney cell lines. Offers protection against polyglutamine-induced death in SK-N-SH and COS-7 cells and attenuates hypoxia-induced apoptosis in VSMC and COS-7 cells. Shown to reduce phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression in hepatoma cells. Promotes the survival of CLL lymphocytes via Wnt/β-catenin-mediated transcription activation. Exhibits delayed cardioprotection in vivo in a rat model via a KATP (ATP-sensitive potassium channels) and MPTP (mitochondrial permeability transition pore)-dependent mechanism at reperfusion.
A cell-permeable (aryl,indole) maleimide compound that acts as a potent, selective, ATP-competitive inhibitor of GSK-3 activity (K_i = 9.1 nM for GSK-3α). At 10 µM concentration, does not significantly inhibit a panel of 24 other protein kinases tested. Reported to stimulate glycogen synthesis in Chang human liver cells (EC₅₀ = 3.6 µM) and induce transcription of β-catenin-LEF/TCF (lymphoid enhancer factor/T cell factor) regulated reporter gene in HEK293 human embryonic kidney cell lines. Offers protection against polyglutamine-induced death in SK-N-SH and COS-7 cells and attenuates hypoxia-induced apoptosis in VSMC and COS-7 cells. Shown to reduce phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression in hepatoma cells. Promotes the survival of CLL lymphocytes via Wnt/β-catenin-mediated transcription activation. Exhibits delayed cardioprotection in vivo in a rat model via a KATP (ATP-sensitive potassium channels) and MPTP (mitochondrial permeability transition pore)-dependent mechanism at reperfusion.

包装

10 mg in Glass bottle

警告

Toxicity: Irritant (B)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

其他说明

Gross, E., et al. 2008. Am. J. Phy. Heart Circ Physiol.294, H1497.
Bain, J., et al. 2007. Biochem. J.408, 297.
Lu, D., et al. 2004. PNAS.101, 3118.
Carmichael, J., et al. 2002. J. Biol. Chem.277, 33791.
Culbert, A.A., et al. 2001. FEBS Lett.507, 288.
Lochhead, P.A., et al. 2001. Diabetes50, 937.
Cross, D.A., et al. 2001. J. Neurochem.77, 94.
Coghlan, M.P., et al. 2000. Chem. Biol.7, 793.

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

基本信息

安全信息

图形或危害标志
危险性说明	H315: Causes skin irritation. H319: Causes serious eye irritation. H335: May cause respiratory irritation.
防范说明	P233: Keep container tightly closed. P260: Do not breathe . P261: Avoid breathing . P264: Wash hands thoroughly after handling. P271: Use only outdoors or in a well-ventilated area. P280: Wear . P302 + P352: IF ON SKIN: Wash with plenty of soap and water. P304: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.. P304 + P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P321: Specific treatment (see relevant procedures. on this label). P332 + P313: If skin irritation occurs: Get medical advice/ attention. P337 + P313: If eye irritation persists: Get medical advice/attention. P340: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P362: Take off contaminated clothing and wash before reuse. P403: Store in a well-ventilated place. P403 + P233: Store in a well-ventilated place. Keep container tightly closed. P405: Store locked up. P501: Dispose of contents/container to in accordance with local regulation .