Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem- and progenitor cells in acute myeloid leukemia AML. Herrmann et al. Oncotarget. [Epub ahead of print], 2012;3:1588 Small-molecule inhibition of BRDT for male contraception. ...
JQ1 is a wonder therapeutic molecule that selectively inhibits the BRD4 signaling pathway and is thus widely used in the anticancer drug discovery program. Due to its unique selective BRD4 binding property, its applications are further extended in the design and synthesis of bi-functional PROTAC ...
The bromodomain and extra C-terminal domain (BET) is a family of proteins containing tandem Brd motifs (most importantly,BRD2, BRD3,BRD4, and BRDT). BET proteins act as epigenetic readers, recruiting other proteins to the chromatin in regions with lysine-acetylatedhistones(Dawson, Kouzarides, ...
Corneal scarring is characterized by the improper deposition of extracellular matrix components and myofibroblast differentiation from keratocytes. The bromodomain-containing protein 4 (BRD4) inhibitor JQ1 has been shown to attenuate pathological fibrosi
Analysis of published data sets26,31 identified that many of the hypoxic JQ1-regulated genes have BRD4 binding and that 14% of the genes simultaneously upregulated by hypoxia, down- regulated by JQ1 and bound by BRD4 are direct targets of either HIF-1α or HIF-2α; these included VEGFA ...
JQ1, a first-in-class potent and selective inhibitor of Bromodomain-containing protein 4 (BRD4), displaces Bro- modomain and Extraterminal (BET) bromodomains from chromatin and interferes with BRD4 function [9]. JQ1 is widely used for studying tumor biology, inflammation, and other research [...
Recently, it has been suggested that BRD4 may positively modulate necroptosis and suppress BRD4 via its selective inhibitor JQ1 and so inhibit MLKL-meditated necroptosis. This has been found to contribute to the inhibition of inflammatory response syndrome in rodent animals [15]. Given the critical ...
As a class, ‘BET’ inhibitors disrupt binding of bromodomain and extra-terminal motif (BET) proteins, BRD2, BRD3, BRD4 and BRDT, to acetylated histones preventing recruitment of RNA polymerase 2 to enhancers and promoters, especially super-enhancers, to
Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy Future Sci OA (2019) W. Fiskus et al. Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells Mol. Canc. Therapeut....
In testing our hypothesis, we found that Brd4 is a key co-activator of photostress-augmented iNOS expression. Blocking Brd4 with the BET bromodomain inhibitor JQ1 (34, 35) substantially reduced acquired cell aggressiveness and to a much greater extent than an iNOS enzymatic inhibitor at many ...