EPZ005687

EPZ005687 is a potent and selective inhibitor of EZH2 with K_i of 24 nM, and has 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases. IC50 & Target: Ki: 24 nM (EZH2)^[1] In Vitro: EPZ005687 shows concentration-dependent inhibition of PRC2 enzymatic activity with an IC₅₀?value of 54±5 nM. EPZ005687 specifically inhibits H3K27 methylation in lymphoma cells. EPZ005687 has a notable effect on proliferation of the EZH2Y641F-bearing cell line. EPZ005687 decreases proliferation in mutant but not wild-type EZH2 lymphoma cells^[1]. EPZ005687 (0.5, 1, 5 and 10 μM) induces an obvious apoptosis of U937 cells in a dose-dependent manner. EPZ005687 inhibits obviously the proliferation of U937 cells but has weak effect on the proliferation of NBMCD34⁺ cells. EPZ005687 induces G1 phase blocking and decreases the percentage of cells in S phase in U937 cells. In addition, EPZ005687 produces obviously depletion of H3K27 methylation in U937 cells, but hardly has effect on the H3K27 methylation of NBMCD34⁺ cells^[2].