5DFC

Crystal structure of BRD2(BD2) W370F mutant with ligand I-BET 762 bound

5DFC の概要

• エントリーDOI: 10.2210/pdb5dfc/pdb
• 分子名称: Bromodomain-containing protein 2, GLYCEROL, NONAETHYLENE GLYCOL, ... (6 entities in total)
• 機能のキーワード: transcription factors, bet bromodomains, protein mutation engineering, molecular probes, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : P25440
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14325.54

構造登録者

Tallant, C.,Baud, M.,Lin-Shiao, E.,Chirgadze, D.Y.,Ciulli, A. (登録日: 2015-08-26, 公開日: 2015-11-11, 最終更新日: 2024-01-10)

主引用文献

Baud, M.G.,Lin-Shiao, E.,Zengerle, M.,Tallant, C.,Ciulli, A.
New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition.
J.Med.Chem., 59:1492-1500, 2016

PubMed Abstract: We describe new synthetic routes developed toward a range of substituted analogues of bromo and extra-terminal (BET) bromodomain inhibitors I-BET762/JQ1 based on the triazolo-benzodiazepine scaffold. These new routes allow for the derivatization of the methoxyphenyl and chlorophenyl rings, in addition to the diazepine ternary center and the side chain methylene moiety. Substitution at the level of the side chain methylene afforded compounds targeting specifically and potently engineered BET bromodomains designed as part of a bump and hole approach. We further demonstrate that marked selectivity for the second over the first bromodomain can be achieved with an indole derivative that exploits differential interaction with an aspartate/histidine conservative substitution on the BC loop of BET bromodomains.

PubMed: 26367539
DOI: 10.1021/acs.jmedchem.5b01135

実験手法

X-RAY DIFFRACTION (1.5 Å)