Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening.

摘要: Bromodomains (BRDs) are epigenetic readers that recognize acetylated-lysine (KAc) on proteins and implicated in a number of diseases. We describe virtual screening approach to identify BRD inhibitors. Key elements this the extensive design use substructure queries compile set commercially available compounds featuring novel putative KAc mimetics docking for final compound selection. validation by applying it first BRD4. The selection testing 143 lead discovery six hits, including four unprecedented mimetics. solved crystal structure determined their binding mode, improved potency through synthesis purchase derivatives. This work provides validated is applicable other BRDs describes can be further explored more potent