A highly potent and selective inhibitor of DOT1L histone methyltransferase activity (Ki = 80 pM); inhibits the H3K79 methylation in various human leukemia cell lines (IC50s = 3-5 nM), decreasing MLL-fusion target gene expression and inhibiting proliferation; intravenous infusion of EPZ-5676 at a dose of 35 mg/kg can regress tumors in a rat xenograft model of MLL-rearranged leukemia.