Valemetostat

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) . (In Vitro) :Valemetostat (1-1000 nM) strongly and specifically inhibits EZH1 and EZH2 with IC50 values <10 nM.Valemetostat (100 nM; 7 d) effectively removes H3K27me3 and also prevents unexpected gain of H3K27me3.Valemetostat (0.1-100 nM; 7 d) potently inhibits H3K27me3 by low-dose treatment in the sensitive lymphoma types. (In Vivo) :Valemetostat (0.01 mg/g; i.p.; once) prevents the changes of H3K27me3 after exercise training.