SKLB-03176 (SKLB03176) is a potent, selective, covalent EZH2 inhibitor with IC50 of 47 nM, covalently binds to the SAM pocket of EZH2.
SKLB-03176 showed good inhibitory activity against mutations EZH2 Y641F, EZH2 Y641N, and EZH2A677G at 200 nM concentration.
SKLB-03176 exhibited weak activity against other targets, such as 5 histone methyltransferases and more than 30 kinases, >50-fold selective for EZH2 over the highly homologous H3K27 methyltransferase EZH1 (IC50=2.45 uM).
SKLB-03176 inhibited the activity of a variety of EZH2 mutants and significantly inhibited the expression of H3K27Me3 in cells.
SKLB-03176 showed no cytotoxicity to normal cells.
