6V1E

Crystal structure of the bromodomain of human BRD7 bound to BI7273

6V1E の概要

• エントリーDOI: 10.2210/pdb6v1e/pdb
• 分子名称: Bromodomain-containing protein 7, 4-[4-[(dimethylamino)methyl]-3,5-dimethoxy-phenyl]-2-methyl-2,7-naphthyridin-1-one, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: brd4, brd, inhibitor, bi7273, gene regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15009.34

構造登録者

Chan, A.,Karim, M.R.,Schonbrunn, E. (登録日: 2019-11-20, 公開日: 2020-03-11, 最終更新日: 2023-10-11)

主引用文献

Karim, R.M.,Chan, A.,Zhu, J.Y.,Schonbrunn, E.
Structural Basis of Inhibitor Selectivity in the BRD7/9 Subfamily of Bromodomains.
J.Med.Chem., 63:3227-3237, 2020

PubMed Abstract: Inhibition of the bromodomain containing protein 9 (BRD9) by small molecules is an attractive strategy to target mutated SWI/SNF chromatin-remodeling complexes in cancer. However, reported BRD9 inhibitors also inhibit the closely related bromodomain-containing protein 7 (BRD7), which has different biological functions. The structural basis for differential potency and selectivity of BRD9 inhibitors is largely unknown because of the lack of structural information on BRD7. Here, we biochemically and structurally characterized diverse inhibitors with varying degrees of potency and selectivity for BRD9 over BRD7. Novel cocrystal structures of BRD7 liganded with new and previously reported inhibitors of five different chemical scaffolds were determined alongside BRD9 and BRD4. We also report the discovery of first-in-class dual bromodomain-kinase inhibitors outside the bromodomain and extraterminal family targeting BRD7 and BRD9. Combined, the data provide a new framework for the development of BRD7/9 inhibitors with improved selectivity or additional polypharmacologic properties.

PubMed: 32091206
DOI: 10.1021/acs.jmedchem.9b01980

実験手法

X-RAY DIFFRACTION (2.3 Å)