| Literature DB >> 24015967 |
Olivier Mirguet1, Romain Gosmini, Jérôme Toum, Catherine A Clément, Mélanie Barnathan, Jean-Marie Brusq, Jacqueline E Mordaunt, Richard M Grimes, Miriam Crowe, Olivier Pineau, Myriam Ajakane, Alain Daugan, Phillip Jeffrey, Leanne Cutler, Andrea C Haynes, Nicholas N Smithers, Chun-wa Chung, Paul Bamborough, Iain J Uings, Antonia Lewis, Jason Witherington, Nigel Parr, Rab K Prinjha, Edwige Nicodème.
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.Entities:
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Year: 2013 PMID： 24015967 DOI： 10.1021/jm401088k
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446