6FFG

Human BRD2 C-terminal bromodomain with (S)-1-(2-cyclopropyl-4-(2-(hydroxymethyl)benzyl)-6-(1,2,3,6-tetrahydropyridin-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

6FFG の概要

• エントリーDOI: 10.2210/pdb6ffg/pdb
• 関連するPDBエントリー: 6FFD 6FFE 6FFF
• 分子名称: Bromodomain-containing protein 2, 1,2-ETHANEDIOL, (S)-1-(2-cyclopropyl-4-(2-(hydroxymethyl)benzyl)-6-(1,2,3,6-tetrahydropyridin-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone, ... (6 entities in total)
• 機能のキーワード: inhibitor, histone, epigenetic reader, bromodomain, brd4, bromodomain containing protein 4, antagonist, transcription
• 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: 14381.62

構造登録者

Chung, C. (登録日: 2018-01-07, 公開日: 2019-01-30, 最終更新日: 2024-05-08)

主引用文献

Law, R.P.,Atkinson, S.J.,Bamborough, P.,Chung, C.W.,Demont, E.H.,Gordon, L.J.,Lindon, M.,Prinjha, R.K.,Watson, A.J.B.,Hirst, D.J.
Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain.
J.Med.Chem., 61:4317-4334, 2018

PubMed Abstract: The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but few reported inhibitors show selectivity within the BET family. Inhibitors with selectivity for the first or second bromodomain are desired to aid investigation of the biological function of these domains. Focused library screening identified a series of tetrahydroquinoxalines with selectivity for the second bromodomains of the BET family (BD2). Structure-guided optimization of the template improved potency, selectivity, and physicochemical properties, culminating in potent BET inhibitors with BD2 selectivity.

PubMed: 29656650
DOI: 10.1021/acs.jmedchem.7b01666

実験手法

X-RAY DIFFRACTION (1.59 Å)