EPZ005687 1396772-26-1
EPZ-005687
分子式:C32H37N5O3 分子量:539.67
产品描述
EPZ005687是有效的,选择性EZH2抑制剂,Ki为24 nM,比作用于EZH1选择性高50倍,比作用于15种其他蛋白甲基转移酶选择性高500倍。
靶点
EZH2
IC50
24 nM (Ki)
体外研究
EPZ005687 shows concentration-dependent inhibition of PRC2 enzymatic activity with an IC50 value of 54 nM. It is a direct inhibitor of PRC2 enzymatic activity and does not function by disrupting the protein-protein interactions among the PRC2 subunits. EPZ005687 binds in the SAM pocket of the EZH2 SET domain and is a SAM-competitive inhibitor of EZH2 enzyme activity. The affinity of EPZ005687 is similar (within a two-fold range) for PRC2 complexes containing wild-type and Tyr641 mutant EZH2, but significantly greater affinity for the A677G mutant enzyme (5.4-fold). EPZ005687 reduces H3K27 methylation in various lymphoma cells. It shows robust cell killing in heterozygous Tyr641 or Ala677 mutant cells, with minimal effects on the proliferation of wild-type cells. EPZ005687 increases G1 phase of the cell cycle with correlative decreases in the S as well as the G2/M phases. In a Tyr641 mutant lymphoma cell line, EPZ005687 can lead to derepression of known EZH2 target genes and affect genes specifically repressed by the EZH2 Tyr641 mutant.
体内研究
溶解性
DMSO 2 mg/mL,水 <1 mg/mL,乙醇 <1 mg/mL
稳定性
2年 -20°C粉状,6月-80°C溶于DMSO