产品说明书

SB-216763

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Chemical Structure| 280744-09-4 同义名 : -
CAS号 : 280744-09-4
货号 : A100785
分子式 : C19H12Cl2N2O2
纯度 : 98%
分子量 : 371.217
MDL号 : -
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(282.85 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 39 mg/mL suspension

生物活性
靶点

  • GSK-3α

    GSK-3α, IC50:34.3 nM

  • GSK-3β

    GSK-3β, IC50:~34.3 nM
描述 GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3 and subunit, which plays a key role in many different biological processes including tumorigenesis, cell survival, and developmental patterning. GSK-3 is constitutively active in non-stimulated cells and can negatively regulate canonical Wnt/-catenin signaling[2][3]. SB-216763 is a maleimide-derived GSK-3 inhibitor with IC50 value of 34nM for GSK-3K (measured by recombinant human GSK-3K). SB-216763 is equally effective at inhibiting GSK-3 and SB-216763<6uM can induce transcription of a-catenin-LEF/TCF regulated reporter gene dose-dependently in serum starved HEK293 for 16h [1]. Treatment with 5uM SB-216763 for 4h can increase levels of cytoplasmic-catenin, which is a target negatively regulated by GSK-3, in both serum-starved cerebellar granule neurons and HEK293 cells. SB-216763 (3-5uM) can confer a marked reduction in GSK-3-dependent tau phosphorylation at Ser202-phosphoepitopes in transfected HEK293 cells and endogenous tau protein in cerebellar granule neurons[4]. SB-216763 can cross the blood–brain barrier and enter the CNS in both rodents and nonhuman primates[5]. Co-infusion of SB-216763 corrected all responses to Aβ infusion except the induction of gliosis and behavioral deficits in the Morris water maze of rats [6].
作用机制 Mechanism: SB-216763 can inhibit GSK-3 in an ATP competitive manner. [1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK293 cells Function assay Glycogen synthase activity of HEK293 cells, inhibition of GSK3-beta, EC50=0.2 μM 12941331
human 5637 cell Growth inhibition assay Inhibition of human 5637 cell growth in a cell viability assay, IC50=25.8111 μM SANGER
human A101D cell Growth inhibition assay Inhibition of human A101D cell growth in a cell viability assay, IC50=30.9784 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.47mL

2.69mL

1.35mL

26.94mL

5.39mL

2.69mL
参考文献

[1]Coghlan MP, Culbert AA, 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.

[2]Martinez A, Castro A, et al. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev. 2002 Jul;22(4):373-84.

[3]Domoto T, Pyko IV, et al. Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy. Cancer Sci. 2016 Oct;107(10):1363-1372.

[4]Cross DA, Culbert AA, et al. Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem. 2001 Apr;77(1):94-102.

[5]Li L, Shao X, et al. Synthesis and Initial in Vivo Studies with [(11)C] SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3. ACS Med Chem Lett. 2015 Mar 10;6(5):548-52.

[6]Hu S, Begum AN, et al. GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adve