The evident promise of DOT1L inhibition for the treatment of MLL-rearranged leukaemias led Epizyme to continue building on EPZ004777, eventually developing EPZ-5676, or pinometostat (Fig. 12).142,143 Reversion to an adenine scaffold over a deazapurine, the introduction of a cyclobutyl-based linker, and the recapitulation of the urea pharmacophore with a benzimidazole scaffold led to marked improvements over EPZ004777. Here, KMT2A is linked to leukemia.