T. Keates

TL;DR: A cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains is reported, establishing proof-of-concept for targeting protein–protein interactions of epigenetic ‘readers’, and providing a versatile chemical scaffold for the development of chemical probes more broadly throughout the b romodomain family.

TL;DR: Bromodomains are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks, and a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4 is uncovered.

TL;DR: The presented data offer a model for the quaternary assembly of this E3 class that supports the bivalent capture of Nrf2 and reveals potential new sites for E3 inhibitor design.

TL;DR: High-throughput assays that quantify the binding of bromodomains to acetylated histone peptides are reported, and it is demonstrated that these assays can be used to detect small molecule binding from the very weak to the nanomolar range.

TL;DR: This new series of compounds is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily and are valuable starting points for discovery of selective bRomodomain inhibitors and inhibitors with mixed bromidomain pharmacology.