Bromodomains: a new target class for small molecule drug discovery

The recent disclosure of potent, selective small molecule inhibitors (I-BET762, I-BET151 and JQ1) of the BET family of bromodomains demonstrate that epigenetic reader proteins may be as tractable to small molecule drug discovery as their epigenetic enzyme counterparts. Here we review these latest findings, strategies that have been successful in identifying bromodomain (BD) inhibitors and the disease association of bromodomain containing proteins (BCPs) which may offer opportunities for therapeutic intervention.

► Potent, selective and cell permeable small molecule bromodomain inhibitors of the BET family of proteins have been discovered. ► These compounds demonstrate profound in vivo effects in murine models of sepsis, NUT midline carcinoma and AML. ► The druggable genome should be extended to include epigenetic reader domains such as bromodomains. ► Current strategies for finding bromodomain inhibitors and opportunities in other disease areas are summarised.