RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain
Picaud S., Wells C., Felletar I., Brotherton D., Martin S., Savitsky P., Diez-Dacal B., Philpott M., Bountra C., Lingard H., Fedorov O., Müller S., Brennan PE., Knapp S., Filippakopoulos P.
SignificanceBromo and extraterminal (BET) proteins have diverse roles in regulating tissue-specific transcriptional programs, raising safety concerns for their inhibition and suggesting that targeting of specific isoforms or even specific domains within this subfamily is important. We report the discovery and characterization of RVX-208 as a domain-selective inhibitor of BETs and provide a potential mechanism of action of a clinical compound that was identified based on phenotypic screens.