7B1T

Crystal structure of BRD4(1) in complex with the inhibitor MPM6

7B1T の概要

• エントリーDOI: 10.2210/pdb7b1t/pdb
• 分子名称: Bromodomain-containing protein 4, 3-(5-azanyl-2-chloranyl-phenyl)-1-methyl-4,7-dihydro-2~{H}-cyclohepta[c]pyrrol-8-one, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: brd4, brd4(1), bet, mpm6, bromodomain, inhibitor, co-crystal, cocrystal, fragment, protein binding
• 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: 15542.40

構造登録者

Huegle, M. (登録日: 2020-11-25, 公開日: 2022-06-08, 最終更新日: 2024-02-07)

主引用文献

Warstat, R.,Pervaiz, M.,Regenass, P.,Amann, M.,Schmidtkunz, K.,Einsle, O.,Jung, M.,Breit, B.,Hugle, M.,Gunther, S.
A novel pan-selective bromodomain inhibitor for epigenetic drug design.
Eur.J.Med.Chem., 249:115139-115139, 2023

PubMed Abstract: For a long time, the development of bromodomain (BD) inhibitors (BDi) was almost exclusively related to the BET family. More recently, BDi for BDs outside the BET family have also been developed. Here we present a novel pan-BDi with micromolar affinities to various BDs, and nanomolar affinities to representatives of BD families I, II (Bromodomain and Extra-Terminal Domain (BET) family), III, and IV. The inhibitor shows a broad activity profile with nanomolar growth inhibition (GI50) values on various cancer cell lines. Subsequently, we were able to control the selectivity of the inhibitor by simple modifications and turned it into a highly selective BRD9 inhibitor.

PubMed: 36736153
DOI: 10.1016/j.ejmech.2023.115139

実験手法

X-RAY DIFFRACTION (1.92 Å)