PerspectiveTargeting the transcription factor Myb by small-molecule inhibitors

- The transcription factor Myb is an emerging drug target for leukemia therapy.
- Initial work has identified several Myb-inhibitory compounds providing proof of principle that targeting Myb is feasible.
- Small-molecule suppression of Myb activity preferentially inhibits the proliferation of leukemic versus normal hematopoietic cells.

The transcription factor Myb is a key regulator of hematopoietic cell proliferation, differentiation, and survival and has been implicated in the development of leukemia and several other human cancers. Pharmacological inhibition of Myb is therefore emerging as a potential therapeutic strategy. Recently, the first low-molecular-weight compounds that show Myb inhibitory activity have been identified. Characterization of these compounds suggests disruption of the protein-protein-interaction of Myb and the coactivator p300 as a suitable strategy to inhibit Myb.