Design, synthesis, and biological activity of 1,2,3-Triazolobenzodiazepine BET Bromodomain inhibitors
Publication Year 2017-12-14,Volume 8,Issue #12,Page 1298-1303
Journal Title
ACS Med Chem Lett
Publication Type
Journal Article
A number of diazepines are known to inhibit bromo- and extra-terminal domain (BET) proteins. Their BET inhibitory activity derives from the fusion of an acetyl-lysine mimetic heterocycle onto the diazepine framework. Herein we describe a straightforward, modular synthesis of novel 1,2,3-triazolobenzodiazepines and show that the 1,2,3-triazole acts as an effective acetyl-lysine mimetic heterocycle. Structure-based optimization of this series of compounds led to the development of potent BET bromodomain inhibitors with excellent activity against leukemic cells, concomitant with a reduction in c-MYC expression. These novel benzodiazepines therefore represent a promising class of therapeutic BET inhibitors.
WEHI Research Division(s)
Chemical Biology; Cancer And Haematology; Systems Biology And Personalised Medicine; Bioinformatics; Structural Biology
PubMed ID
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Creation Date: 2018-01-15 12:39:46
Last Modified: 2018-01-15 12:41:48
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