EPZ005687

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Chemical Structure| 1396772-26-1 同义名 : -
CAS号 : 1396772-26-1
货号 : A553761
分子式 : C32H37N5O3
纯度 : 98+%
分子量 : 539.67
MDL号 : MFCD25372029
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 8 mg/mL(14.82 mM)，配合低频超声，并水浴加热至45℃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
生物活性
靶点

  • Histone Methyltransferase

    EZH2, Ki:24 nM
描述 EZH2 is the enzymatically active core subunit of the PRC2 complex, which methylates H3K27 and facilitates chromatin compaction and gene silencing. EPZ005687 is a potent inhibitor of PRC2 with IC50 value of 54±5nM (measured by PRC2 enzymatic activity), with selectivity >500-fold over other HMTs, ~50-fold over EZH1. EPZ005687 can specifically inhibit H3K27 methylation. Treatment with EPZ005687 (0.044-5.6uM) for 96h shows a dose-dependent decrease in H3K27me3 in wild-type EZH2 lymphoma cell line OCI-lY19. EPZ005687 can decrease proliferation in a dose (<8.3uM) and time (<11 days) dependent manner in mutant EZH2 lymphoma cells, WSU-DLCL2 (Y641F) and pfeiffer (A677G), but not wild-type cells, OCI-lY19 cell line. Treatment in mutant EZH2 lymphoma cells, WSU-DLCL2 (Y641F), with EPZ005687 (0.2-6uM) for 4 days resulted in a dose-dependent increase of accumulation in G1[1]. Recently, it was found that EPZ005687 (10mg/kg, injected peritoneally, once a week for 4 weeks) can significantly inhibit the development of TAC (Transverse Aortic Constriction) -induced PAH (pulmonary artery hypertension) in an EZH2-SOD1-ROS dependent manner in male balb/c mice (6–8 weeks old) [2].
作用机制 EPZ005687 is a SAM-competitive inhibitor of PRC2, which binds in the SAM pocket of the EZH2 SET domain.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
human OCI-LY19 cells Function assay 96 h Inhibition of wild-type EZH2 in human OCI-LY19 cells assessed as reduction of H3K27me3 level after 96 hrs by ELISA assay, IC50=0.08 μM 25406853
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.85mL

0.37mL

0.19mL

9.26mL

1.85mL

0.93mL

18.53mL

3.71mL

1.85mL
参考文献

[1]Knutson SK, Wigle TJ, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6.

[2]Shi ZL, Fang K, et al. EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice. Can Respir J. 2018 Feb 28;2018:9174926.