5LJ2

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 5-(5-aminopyridin-3-yl)-8-(((3R,4R)-3-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methoxy)piperidin-4-yl)amino)-3-methyl-1,7-naphthyridin-2(1H)-one

5LJ2 の概要

• エントリーDOI: 10.2210/pdb5lj2/pdb
• 分子名称: Bromodomain-containing protein 4, 1,2-ETHANEDIOL, 5-(5-aminopyridin-3-yl)-8-(((3R,4R)-3-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methoxy)piperidin-4-yl)amino)-3-methyl-1,7-naphthyridin-2(1H)-one, ... (4 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)
• 細胞内の位置: Nucleus: O60885
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15798.21

構造登録者

Chung, C.,Bamborough, P.,Demont, E. (登録日: 2016-07-17, 公開日: 2016-08-31, 最終更新日: 2024-05-08)

主引用文献

Bamborough, P.,Chung, C.W.,Demont, E.H.,Furze, R.C.,Bannister, A.J.,Che, K.H.,Diallo, H.,Douault, C.,Grandi, P.,Kouzarides, T.,Michon, A.M.,Mitchell, D.J.,Prinjha, R.K.,Rau, C.,Robson, S.,Sheppard, R.J.,Upton, R.,Watson, R.J.
A Chemical Probe for the ATAD2 Bromodomain.
Angew.Chem.Int.Ed.Engl., 55:11382-11386, 2016

PubMed Abstract: ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

PubMed: 27530368
DOI: 10.1002/anie.201603928

実験手法

X-RAY DIFFRACTION (1.19 Å)