7VD4

Crystal structure of BPTF-BRD with ligand TP248 bound

7VD4 の概要

• エントリーDOI: 10.2210/pdb7vd4/pdb
• 分子名称: Nucleosome-remodeling factor subunit BPTF, 6-[4-[3-(dimethylamino)propoxy]phenyl]-N-methyl-2-methylsulfonyl-pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: bptf bromodomain, lysine acetylation, small-molecule inhibitor, biosynthetic protein, antitumor protein
• 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: 13750.75

構造登録者

Lu, T.,Lu, H.B. (登録日: 2021-09-06, 公開日: 2022-09-14, 最終更新日: 2023-11-29)

主引用文献

Lu, H.,Lu, T.,Zu, S.,Duan, Z.,Guang, Y.,Li, Q.,Ma, J.,Chen, D.,Li, B.,Lu, W.,Jiang, H.,Luo, C.,Ye, D.,Chen, K.,Lin, H.
Discovery of a highly potent CECR2 bromodomain inhibitor with 7H-pyrrolo[2,3-d] pyrimidine scaffold.
Bioorg.Chem., 123:105768-105768, 2022

PubMed Abstract: Cat eye syndrome chromosome region candidate 2 (CECR2) bromodomain is a module of CECR2-containing remodeling factor (CERF), which is a chromatin remodeling complex correlating with transcriptional control and adjustment of chromatin architecture. Potent chemical probes would be beneficial to gain insights into the biochemical and pharmacological functions of CECR2 BRD. Herein, we report the discovery of a series of CECR2 BRD inhibitors with 7H-pyrrolo[2,3-d] pyrimidine scaffold based on molecular docking model of TP-248 and CECR2 BRD. The most potent inhibitor of this series, DC-CBi-22 with IC of 8.0 ± 1.4 nM against CECR2 BRD and selectivity over BPTF BRD up to 24.9-fold. The SARs were detailed according to molecular docking. DC-CBi-22 would serve as a useful chemical probe for the study of CECR2.

PubMed: 35378372
DOI: 10.1016/j.bioorg.2022.105768

実験手法

X-RAY DIFFRACTION (1.85659146555 Å)