DiscussionWe recently reported that several clinical kinase inhibitors also inhibit bromodomain epigenetic reader proteins with therapeutically relevant potencies (Nat. Chem. Biol. (2014) doi: 10.1038/nchembio.1471). Nanomolar activity on BRD4 by BI-2536 and TG-101348, clinical PLK1 and JAK2/FLT3 kinase inhibitors, respectively, was particularly noteworthy as these combinations of activities on independent oncogenic pathways exemplify a novel strategy for rational single agent polypharmacological targeting. Furthermore, structure-activity relationships and co-crystal structures identified design features that enable a general platform for the rational design of dual kinase-bromodomain inhibitors. Here we present data from the DiscoveRx KINOMEscan and BROMOscan platforms that demonstrate feasibility for the rational design of dual inhibitors that target new kinase-bromodomain pairs. These results suggest that the concept of dual kinase-bromo-domain inhibitors can be expanded beyond PLK, JAK2, and FLT3 kinases and beyond BET family bromodomains as well.