Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe.

Several chemical probes have been developed for use in fluorescence polarization screening assays to aid in drug discovery for the bromodomain and extra-terminal domain (BET) proteins. However, few of those have been characterized in the literature. We have designed, synthesized, and thoroughly characterized a novel fluorescence polarization pan-BET chemical probe suitable for high-throughput screening, structure-activity relationships, and hit-to-lead potency and selectivity assays to identify and characterize BET bromodomain inhibitors.