溴尿嘧啶
BRD4
表观遗传学
化学
乙酰化
调节器
BET抑制剂
组蛋白
计算生物学
赖氨酸
药物发现
染色质
生物化学
生物
基因
氨基酸
作者
Olivier Mirguet,Romain Gosmini,Jérôme Toum,Catherine A. Clément,Mélanie Barnathan,Jean‐Marie Brusq,J.E. Mordaunt,Richard M. Grimes,Miriam C. Crowe,Olivier Pineau,Myriam Ajakane,Alain Daugan,Philip D. Jeffrey,Leanne Cutler,Andrea Haynes,Nicholas Smithers,Chun‐wa Chung,Paul Bamborough,Iain Uings,Antonia J. Lewis
摘要
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.
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