5A85

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 8-(3R,4R)-3-(cyclohexylmethoxy)piperidin-4-ylamino-3-methyl-1,2-dihydro-1,7- naphthyridin-2-one

5A85 の概要

• エントリーDOI: 10.2210/pdb5a85/pdb
• 関連するPDBエントリー: 5A81 5A82 5A83
• 分子名称: BROMODOMAIN-CONTAINING PROTEIN 4, 1,2-ETHANEDIOL, (3R,4R)-3-(cyclohexylmethoxy)piperidin-4-yl]amino}-3-methyl-1,2-dihydro-1,7-naphthyridin-2-one, ... (4 entities in total)
• 機能のキーワード: hydrolase, inhibitor, histone, epigenetic reader, bromodomain, brd4, bromodomain containing protein 4, antagonist
• 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: 15531.94

構造登録者

Chung, C.,Bamborough, P.,Demont, E. (登録日: 2015-07-11, 公開日: 2015-08-12, 最終更新日: 2024-05-08)

主引用文献

Bamborough, P.,Chung, C.,Furze, R.C.,Grandi, P.,Michon, A.,Sheppard, R.J.,Barnett, H.,Diallo, H.,Dixon, D.P.,Douault, C.,Jones, E.J.,Karamshi, B.,Mitchell, D.J.,Prinjha, R.K.,Rau, C.,Watson, R.J.,Werner, T.,Demont, E.H.
Structure-Based Optimization of Naphthyridones Into Potent Atad2 Bromodomain Inhibitors.
J.Med.Chem., 58:6151-, 2015

PubMed Abstract: ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.

PubMed: 26230603
DOI: 10.1021/ACS.JMEDCHEM.5B00773

実験手法

X-RAY DIFFRACTION (1.72 Å)