4C66

Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

4C66 の概要

• エントリーDOI: 10.2210/pdb4c66/pdb
• 関連するPDBエントリー: 4C67
• 分子名称: BROMODOMAIN-CONTAINING PROTEIN 4, 4-(2-chlorophenyl)-2-ethyl-9-methyl-6,8-dihydrothieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-10-ium (3 entities in total)
• 機能のキーワード: cell cycle, transcription regulation, inhibitor, epigenetic reader, 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: 15314.12

構造登録者

Chung, C.,Mirguet, O. (登録日: 2013-09-17, 公開日: 2013-10-02, 最終更新日: 2024-05-08)

主引用文献

Mirguet, O.,Gosmini, R.,Toum, J.,Clement, C.,Barnathan, M.,Brusq, J.,Mordaunt, J.E.,Grimes, R.,Crowe, M.,Pineau, O.,Ajakane, M.,Daugan, A.,Jeffrey, P.,Cutler, L.,Haynes, A.,Smithers, N.,Chung, C.,Bamborough, P.,Uings, I.J.,Lewis, T.,Witherington, J.,Parr, N.,Prinjha, R.,Nicodeme, E.
Discovery of Epigenetic Regulator I-Bet762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the Bet Bromodomains.
J.Med.Chem., 56:7501-, 2013

PubMed Abstract: The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

PubMed: 24015967
DOI: 10.1021/JM401088K

実験手法

X-RAY DIFFRACTION (1.87 Å)