Pharmacological Modulation of BET Family in Sepsis

Nian Wang, Runliu Wu, Paul B. Comish, Rui Kang, Daolin Tang

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis 3.0) recommended defining sepsis as a life-threatening organ dysfunction caused by the host's uncontrolled response to infection. The bromodomain and extra-terminal (BET) protein family (such as BRD2, BRD3, and BRD4), an epigenetic regulator of gene transcription, has recently been recognized as a significant septic regulator of inflammation and immune response, including cytokine and chemokine production. Mechanistically, the two N-terminal conserved tandem bromodomains (namely the first bromodomain [BD1] and the second bromodomain [BD2]) favor the binding of BETs to acetylated histones or transcription factors, thereby initiating gene transcription machinery after CycT1 and CDK9 (also known as P-TEFb) are recruited to gene promoters to phosphorylate RNA pol II. Notably, BD1 and BD2 are not functionally redundant because they have different target genes in innate immune cells. Small-molecule BET inhibitors (BETis) for different BDs, such as I-BET, JQ1, I-BET151, apabetalone, RVX-297, and dBET1 have shown promising therapeutic effects in experimental sepsis models. This mini-review summarizes the emerging roles of BETs and the applications of BETis in sepsis, discusses the existing shortcomings of BETis, and introduces possible future research directions in this area.

Original languageEnglish (US)
Article number642294
JournalFrontiers in Pharmacology
StatePublished - Mar 11 2021


  • bromodomain and extra-terminal
  • inflammation
  • inhibitor
  • innate immune
  • sepsis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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