BBDDL2059 (BBDDL 2059) is a potent, selective and covalent inhibitor of EZH2 with IC50 of 1.5 nM (EZH2-Y641F), targeting the Cys663 of EZH2.
BBDDL2059 demonstrates excellent cellular potency with IC50 values of 0.064 and 0.022 μM in inhibition of KARPAS-422 and Pfeiffer cell growth, respectively.
BBDDL2059 shows no significant inhibitionagainst a panel of 10 methyltransferases at 10 uM, including DNA methyltransferase DNMT1, arginine methyltransferases (PRMT1, PRMT4, and PRMT5), and protein lysine methyltransferases (G9a, GLP, MLL1, and MLL4).
BBDDL2059 (0.05-1 uM) effectively reduced the H2K27me3 mark in a concentration- and time- dependent manner but had no effect on the total H3 and EZH2 in KARPAS-422 cells.
