EPZ004777

EPZ004777 is a potent, selective, small-molecule inhibitor of DOT1L with IC50 of 0.4 nM. EPZ004777 selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes. EPZ004777 suppressed expression of leukemogenic genes such as Hoxa cluster genes and Meis1, and selectively impaired proliferation of MLL-AF10 and CALM-AF10 transformed cells. In vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model.