English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Significance BRD4, a major BET family protein, regulates gene transcription through coordinated binding of its characteristic tandem bromodomains (BrDs) to lysine-acetylated histones and transcription factors. Studies show that BRD4 function in transcriptional regulation is likely context- and cell-type-dependent, consistent with the observation that pan-BET BrD inhibitors such as JQ1 are much less effective in solid tumors than in hematopoietic cancers. Here, we show that spatially constrained bivalent inhibition of BRD4 BrDs with our BET inhibitor MS645 results in a sustained repression of BRD4 transcriptional activity in solid-tumor cells including triple-negative breast cancer (TNBC) cells. Our study offers a therapeutic strategy to maximally control BRD4 activity required for rapid cell proliferation of the devastating TNBC that lacks targeted therapy.

Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth