DOT1L and acute lymphoblastic leukemia: EPZ004777 was the first identified selective inhibitor of DOT1L and selectively kills MLL-translocated cells over those without MLL translocation.645 However, due to its poor pharmacokinetic properties, a second generation of EPZ004777, EPZ-5767, was developed with a cyclobutyl ring replacing the ribose moiety.646 EPZ-5767 also shows synergistic effects with cytarabine, daunorubicin, and the DNMT inhibitor azacitidine in treatments for ALL with MLL translocation.