Dated: Apr 13, 2023
Publication Name: Biological and Medicinal Chemistry
Citations : Rational design and development of selective BRD7 bromodomain inhibitors and their activity in prostate cancer
Bromodomain-containing proteins are readers of acetylated lysine and play important roles in cancer. Bromo-domain-containing protein 7 (BRD7) has been implicated in multiple malignancies; however, there are no selective chemical probes to study its function in disease. Using crystal structures of BRD7 and BRD9 bromodomains (BDs) bound to BRD9-selective ligands, we identified a binding pocket exclusive to BRD7. We synthesized a se-ries of ligands designed to occupy this binding region and identified two BRD7-selective inhibitors, 1-78 and 2-77, that bind with nanomolar affinity to the BRD7 BD.
Contributors: Sandra Ordonez ,Chad Maschinot ,Sijie Wang ,Surbhi Sood ,Brayden Strohmier ,Alexander McQuade ,Brian Smith ,Emily Dykhuizen