A DOT1L inhibitor (IC50 = 0.3 nM); selective for DOT1L over a panel of 12 additional protein methyltransferases, DNMT1, and a panel of 29 receptors and ion channels; reduces H3K79me2 levels in MCF-10A breast cancer cells (IC50 = 8.8 nM); selectively reduces the viability of isolated human cord blood cells transformed with an MLL-AF9 fusion oncogene over those transformed with a TLS-ERG fusion oncogene at 1 and 5 µM; adoptive transfer of isolated human CD3+ T cells pre-incubated with SGC0946 (0.5 µM) prevents weight loss, increases survival, and reduces hepatic and colonic lymphocyte infiltration in a xenogeneic mouse model GVHD