Zeprumetostat

An EZH2 inhibitor (IC50 = 0.87 nM for the wild-type enzyme), selective for EZH2 over a panel of 24 histone and DNA methyltransferases (IC50s = >10,000 nM for all) but also inhibits EZH1 (IC50 = 19.1 nM), inhibits EZH2Y641C, EZH2Y641F, EZH2Y641N, EZH2Y641S, and EZH2Y641G (IC50s = 16.8, 2.68, 1.79, 5.07, and 1.13 nM, respectively), reduces H3K27Me3 levels in Pfeiffer DLBCL cells (IC50 = 1.63 nM) and induces cell cycle arrest at the G1 phase and apoptosis in the same cells, reduces tumor growth in PDX mouse models of DLBCL at 60 and 120 mg/kg in combination with HBI 8000. SMILES: CC(NC1=O)=CC(C)=C1CNC(C2=C3C(OC(CN4CCCCC4)=C3)=CC(N(CC)C5CCOCC5)=C2CC)=O. InChi Code: InChI=1S/C32H44N4O4/c1-5-25-28(36(6-2)23-10-14-39-15-11-23)18-29-26(17-24(40-29)20-35-12-8-7-9-13-35)30(25)32(38)33-19-27-21(3)16-22(4)34-31(27)37/h16-18,23H,5-15,19-20H2,1-4H3,(H,33,38)(H,34,37). InChi Key: YLZVNQZYAYVUCW-UHFFFAOYSA-N