BET bromodomain inhibitors

Lysine acetylation creates docking sites for epigenetic reader domains of BET bromodomain proteins that have emerged as principal regulators of linage specific gene transcription. The development of potent and highly selective inhibitors, that have been soon widely available, enabled mechanistic studies in a diversity of disease models leading to a rapid translation into the clinic. Initial studies on pan-BET inhibitors lead now to second generation inhibitors with improved domain selectivity, but also to highly potent bifunctional and dual inhibitors extending the toolbox for basic research on acetylation dependent transcription, BET associated diseases and further translational efforts targeting this interesting family of epige-netic reader domains.

Automated summary

Lysine acetylation creates docking sites for epigenetic reader domains of BET bromodomain proteins, which are important regulators of linage specific gene transcription. The development of potent and selective inhibitors has facilitated mechanistic studies in disease models and translation into clinical practice. Advances in pan-BET inhibitors have led to second generation inhibitors with improved selectivity, as well as highly potent bifunctional and dual inhibitors, expanding the toolbox for research on acetylation dependent transcription, BET-associated diseases, and epigenetic reader domains.