Portal de Periódicos da CAPES

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

2013; American Chemical Society; Volume: 56; Issue: 19 Linguagem: Inglês

10.1021/jm401088k

1520-4804

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, Jason Witherington, Nigel J. Parr, Rab K. Prinjha, Edwige Nicodème,

Multiple Myeloma Research and Treatments

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.