1 research outputs found
Discovery of Epigenetic Regulator IāBET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains
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 structureāactivity 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