CAS NO: | 264218-23-7 |
包装 | 价格(元) |
10mM (in 1mL DMSO) | 电议 |
10mg | 电议 |
50mg | 电议 |
Physical Appearance | A solid |
Storage | Store at RT |
M.Wt | 359.73 |
Cas No. | 264218-23-7 |
Formula | C16H10ClN3O5 |
Solubility | insoluble in H2O; ≥18 mg/mL in DMSO; ≥44.9 mg/mL in EtOH with ultrasonic |
Chemical Name | 3-(3-chloro-4-hydroxyanilino)-4-(2-nitrophenyl)pyrrole-2,5-dione |
Canonical SMILES | C1=CC=C(C(=C1)C2=C(C(=O)NC2=O)NC3=CC(=C(C=C3)O)Cl)[N+](=O)[O-] |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
SB415286是糖原合酶激酶-3(GSK-3)强效选择性的细胞渗透性抑制剂,Ki值为31 nM,对GSK-3和GSK3β效力相当[1]。
在人肝细胞中,SB415286抑制GSK3的活性,促进糖原合成,在HEK293细胞中,SB415286诱导连环蛋白-LEF / TCF调节的报告基因的表达[1]。在原代神经元中,它可以阻止PI3K途径诱导的细胞死亡[2]。进一步研究发现,SB415286降低GSK3β的活性,抑制雷帕霉素(rapamycin)介导的细胞周期蛋白D1下调、细胞周期停滞和化学敏感性[3]。GSK-3β的药物抑制大幅度损伤了p53依赖性的p21和Puma的转录激活,易化了p53依赖性的Bax的构象激活,最终导致p53介导的损伤应答从细胞周期停滞转化为细胞凋亡[4]。SB-415286通过线粒体相关机制减少缺血再灌注损伤。SB-415286减少腺嘌呤核苷酸转运和VDAC的磷酸化,增加Bcl-2与线粒体结合,阻止心肌中线粒体通透性转换孔开放[5]。在辐射诱导的细胞凋亡中,SB-415286对海马神经元产生保护作用。SB-415286抑制GSK-3β,可能会导致MDM2的上调,反过来调节p53的降解和p53依赖性细胞反应[6]。
在小鼠模型进一步证实,SB415286对辐射诱导的中枢神经系统坏死具有神经保护作用。在辐射前用SB415286处理小鼠,即靶向左半球的单个45-Gy部分,通过在体MRI进行检测,与DMSO处理的小鼠相比,SB415286对辐射诱导的坏死具有显著的的保护作用[7]。
参考文献:
Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol. 2000 Oct;7(10):793-803.
Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem. 2001 Apr;77(1):94-102.
Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity. Cancer Res. 2005 Mar 1;65(5):1961-72.
Pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct Bax-mediated mitochondrial pathway in colorectal cancer cells. Cancer Res. 2005 Oct 1;65(19):9012-20.
Glycogen synthase kinase 3 inhibition slows mitochondrial adenine nucleotide transport and regulates voltage-dependent anion channel phosphorylation. Circ Res. 2008 Oct 24;103(9):983-91. doi: 10.1161/CIRCRESAHA.108.178970. Epub 2008 Sep 18.
Glycogen synthase kinase 3β inhibitors protect hippocampal neurons from radiation-induced apoptosis by regulating MDM2-p53 pathway. Cell Death Differ. 2012 Mar;19(3):387-96. doi: 10.1038/cdd.2011.94. Epub 2011 Jul 8.
A GSK-3β inhibitor protects against radiation necrosis in mouse brain. Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):714-21. doi: 10.1016/j.ijrobp.2014.04.018.
Description | SB415286是一种强效的GSK3α抑制剂,IC50和Ki值分别为78 nM和31 nM。 | |||||
靶点 | GSK-3α | GSK-3β | ||||
IC50 | 78 nM (Ki=31 nM) | ~78 nM |