Valemetostat is a dual inhibitor of enhancer of zeste homolog 1 (EZH1) and EZH2.1 It inhibits polycomb repressive complex 2 (PRC2) containing EZH1 or EZH2 as the catalytic subunit in cell-free assays (IC50s = 8.4 and 2.5 nM, respectively). Valemetostat inhibits trimethylation of histone H3 lysine 27 in HCT116 cells (IC50 = 0.44 nM). It inhibits the growth of Karpas-422 diffuse large B cell lymphoma (DLBCL) cells (GI50 = 4.8 nM).
1.Honma, D., Kanno, O., Watanabe, J., et al.Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitorCancer Sci.108(10)2069-2078(2017)