4UIV

BROMODOMAIN OF HUMAN BRD9 WITH N-(1,1-dioxo-1-thian-4-yl)-5-methyl-4- oxo-7-3-(trifluoromethyl)phenyl-4H,5H-thieno-3,2-c-pyridine-2- carboximidamide

4UIV の概要

• エントリーDOI: 10.2210/pdb4uiv/pdb
• 関連するPDBエントリー: 4UIT 4UIU 4UIW 4UIX 4UIY 4UIZ
• 分子名称: BROMODOMAIN-CONTAINING PROTEIN 9, 1,2-ETHANEDIOL, N-(1,1-dioxo-1-thian-4-yl)-5-methyl-4-oxo-7-3-(trifluoromethyl)phenyl-4H,5H-thieno-3,2-c-pyridine-2-carboximidamide, ... (4 entities in total)
• 機能のキーワード: transcription, inhibitor, histone, epigenetic reader
• 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: 12773.80

構造登録者

Chung, C.,Theodoulou, N.T.,Bamborough, P.,Humphreys, P.G. (登録日: 2015-04-03, 公開日: 2015-04-22, 最終更新日: 2024-05-08)

主引用文献

Theodoulou, N.H.,Bamborough, P.,Bannister, A.J.,Becher, I.,Bit, R.A.,Che, K.H.,Chung, C.,Dittmann, A.,Drewes, G.,Drewry, D.H.,Gordon, L.,Grandi, P.,Leveridge, M.,Lindon, M.,Michon, A.,Molnar, J.,Robson, S.C.,Tomkinson, N.C.O.,Kouzarides, T.,Prinjha, R.K.,Humphreys, P.G.
The Discovery of I-Brd9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition.
J.Med.Chem., 59:1425-, 2016

PubMed Abstract: Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain "reader" modules. Inhibitors of the bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition.

PubMed: 25856009
DOI: 10.1021/ACS.JMEDCHEM.5B00256

実験手法

X-RAY DIFFRACTION (1.72 Å)