1300746-52-4Relevant academic research and scientific papers
Discovery of epigenetic regulator i-bet762: Lead optimization to afford a clinical candidate inhibitor of the bet bromodomains
Mirguet, Olivier,Gosmini, Romain,Toum, Jéro?me,Clément, Catherine A.,Barnathan, Mélanie,Brusq, Jean-Marie,Mordaunt, Jacqueline E.,Grimes, Richard M.,Crowe, Miriam,Pineau, Olivier,Ajakane, Myriam,Daugan, Alain,Jeffrey, Phillip,Cutler, Leanne,Haynes, Andrea C.,Smithers, Nicholas N.,Chung, Chun-Wa,Bamborough, Paul,Uings, Iain J.,Lewis, Antonia,Witherington, Jason,Parr, Nigel,Prinjha, Rab K.,Nicodème, Edwige
, p. 7501 - 7515 (2013/11/06)
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.
