A potent and selective DOT1L inhibitor (IC₅₀ = 0. 3 nM in a radioactive enzyme assay); >100-fold selective for other histone methyltransferases (HMTs). SGC0946 also potently reduces H3K79 dimethylation with cellular IC₅₀ of 2.6 nM in A431 cells, and 8.8 nM in MCF10A cells.