SB 216763是有效，选择性和ATP竞争性的 GSK-3

SB 216763 is potent, selective and ATP-competitive GSK-3 inhibitor with IC₅₀s of 34.3 nM for both GSK-3α and GSK-3β.

SB-216763 (10-20 μM) induces β-catenin mediated-transcription in a dose-dependent manner in HEK293 cells. SB-216763 (10, 15 and 20 μM) can maintain mESCs with a pluripotent-like morphology in long-term culture. SB-216763 (10 μM) can maintain J1 mESCs in a pluripotent state for more than a month^[2]. 
SB-216763 inhibits GSK-3 with IC₅₀ of 34 nM^[3].
SB-216763 is equally effective at inhibiting human GSK-3α and GSK-3β^[5].

SB216763 (20 mg/kg, i.v.) significantly improves the survival of BLM-treated mice. Mice randomized to receive BLM plus SB216763 shows a noteworthy reduction, compared with BLM-treated mice. SB216763 (20 mg/kg, i.v.) reduces the magnitude of BLM-induced alveolitis^[1]. SB 216763 (0.2 mg/kg, i.v.) with either 17β-E₁₀₀ or Geni₁₀₀ significantly reduce infarct size when the rabbits' hearts are submitted to 30-min CAO^[4].

371.22

Solid

C₁₉H₁₂Cl₂N₂O₂

280744-09-4

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (269.38 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (insoluble)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 1 years; -20℃, 6 months。-80℃ 储存时，请在 1 年内使用， -20℃ 储存时，请在 6 个月 内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

   

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (6.73 mM); Clear solution

   

  此方案可获得 ≥ 2.5 mg/mL (6.73 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

• 2.

   

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (6.73 mM); Suspended solution; Need ultrasonic

   

  此方案可获得 2.5 mg/mL (6.73 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

• 3.

   

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.73 mM); Clear solution

   

  此方案可获得 ≥ 2.5 mg/mL (6.73 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Gurrieri, et al. 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), a glycogen synthase kinase-3 inhibitor, displays therapeutic properties in a mouse model of pulmonary inflammation and fibrosis. J.Pharmacol.Exp.Ther.2010  [Content Brief]

  [2]. Kirby LA, et al. Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells.PLoS One. 2012;7(6):e39329. Epub 2012 Jun 26.  [Content Brief]

  [3]. Wang M, et al. The first synthesis of [(11)C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3).Bioorg Med Chem Lett. 2011 Jan 1;21(1):245-9. Epub 2010 Nov 11.  [Content Brief]

  [4]. The ceiling effect of pharmacological postconditioning with the phytoestrogen genistein is reversed by the GSK3beta inhibitor SB 216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione] through mitochondrial ATP-dependent potassium channel opening.  [Content Brief]

  [5]. Coghlan MP, et al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol. 2000 Oct;7(10):793-803.  [Content Brief]

  [6]. Wang W, et al. Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition. Toxicol Appl Pharmacol. 2016 Dec 15;313:195-203.  [Content Brief]