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GSK343

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Chemical Structure| 1346704-33-3 同义名 : -
CAS号 : 1346704-33-3
货号 : A135977
分子式 : C31H39N7O2
纯度 : 99%+
分子量 : 541.687
MDL号 : MFCD25563250
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 15 mg/mL(27.69 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：
生物活性
靶点

  • Histone Methyltransferase

    EZH2, IC50:4 nM

    EZH1, IC50:240 nM
描述 EZH2 is the enzymatic subunit of PRC2 (Polycomb repressive complex 2), a complex that can methylate lysine 27 of histone H3 (H3K27) to promote transcriptional silencing. GSK343 is a highly selective EZH2 inhibitor with Kiapp value of 1.2 nM and IC50 value of 174 nM (measured by enzymatic activity in HCC1806 cells), 60-fold more selective to EZH1 and 1000-fold more selective to other methyltransferases tested. Incubation with GSK343 for 72 h led to reduction of H3K27me3 in a dose-dependent manner in HCC1806 breast cancer cells with IC50 value of 174 nM. Greater than 90% inhibition of global H3K27me3 was achieved at higher concentration>1000 nM. Inhibition of EZH2 by GSK343 affected the breast and prostate cancer cell lines tested in 6-day proliferation assay. Among these cells, the prostate cancer cell line LNCaP showed the most sensitive to EZH2 inhibition, with growth IC50 values of 2.9 μM, approximately 20-fold above the IC50 on H3K27me3[1]. GSK343 on concentration of 5 μM can suppress proliferation, migration and invasion and induces G0/G1 arrest in U87 and LN229 glioma cells. Treatment with GSK343 can lead to downregulation of H3K27me3 (5 μM, 4-24 h) in a time-dependent manner and cause a reduction in EZH2, EED and SUZ12 protein levels in U87 and LN229 cells (5 μM, for 48 h). Meanwhile, the expression of the classical EZH2 target genes, including E-cadherin, PTEN and p21, increase in U87 and LN229 cells (5 or 7.5 μM, for 48 h). GSK343 reverses mesenchymal transition in glioma cells and attenuates the stemness of glioma stem cells. Intraperitoneal injections of GSK343 (10 mg/kg) every other day for 28 days inhibited glioma tumorigenesis and invasiveness in nude mice intracranially xenotransplanted with luciferase-expressing U87 glioma cells. Prolonged survival period can be observed on day 45[2].
作用机制 GSK343 is the SAM-competitive inhibitor of PRC2.[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
2D10 0.25-2.0 μM Function Assay 96 h reduces total cellular trimethylated H3K27 in a time- and dose-dependent manner 26041287
A549 0-20 μM Growth Inhibition Assay 72 h shows cytotoxicity in a dose-dependent manner 25203626
A549 10 μM Function Assay 24 h induces autophagy 25203626
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.85mL

0.37mL

0.18mL

9.23mL

1.85mL

0.92mL

18.46mL

3.69mL

1.85mL
参考文献

[1]Verma SK, Tian X, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6.

[2]Yu T, Wang Y, et al. The EZH2 inhibitor GSK343 suppresses cancer stem-like phenotypes and reverses mesenchymal transition in glioma cells. Oncotarget. 2017 Sep 27;8(58):98348-98359.