Combined pharmacophore models as virtual screening protocol against BRD4(1) inhibitor

Bromodomain-containing protein is involved in many essential cellular processes, such as chromosomes for cell cycle progression, cellular viability and embryonic stem cell regulation, which plays a significant role in cancers and lysine acetylation. However, there is no information available regarding the discovery for structurally novel existing BRD4(1) inhibitors up to date. Therefore, we collected reported compounds from GSK library to generate ligand-based pharmacophore and used 11 BRD4(1)-inhibitor co-crystal structures to establish our structure-based pharmacophore for multiple virtual screening of potent BRD4(1) inhibitors. These results may provide important information for further design and optimization of novel BRD4(1) inhibitors in cancer treatment. The results of this study will not only provide a better understanding of BRD4(1) inhibitors interaction, but will also assist the development of new potent hits for BRD4(1).