Bromodomain Drug Discovery - the Past, the Present, and the Future

Chem Rec. 2018 Dec;18(12):1808-1817. doi: 10.1002/tcr.201800074. Epub 2018 Oct 5.


With the bromodomain (BRD) inhibitor JQ1, a remarkable success story of BRD4 as a novel drug target has been set off that yielded many anti-cancer drugs that are now in clinical trials. But not all of the great prospects of BRDs as drug targets may become true. First evaluations of ongoing clinical trials revealed that treatment with BET-inhibitors can be accompanied with significant toxic side effects and the validation of the therapeutic benefit of BET-inhibitors compared to existing therapies is still pending. New strategies that may overcome possible obstacles in BRD drug discovery include combination therapies with other agents, dual target inhibitors, and proteolysis targeting chimeras (PROTACs). Furthermore, non-BET proteins seem promising drug targets as well. Most recently, BRDs have been identified as putative targets to treat parasitic diseases such as malaria. Milestones in BRD drug discovery are reviewed and promising new developments are evaluated.

Keywords: BET-inhibitors; PROTACs; bromodomains; drug discovery; dual target inhibitors; epigenetics.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Azepines / chemistry
  • Azepines / metabolism
  • Cell Cycle Proteins
  • Drug Discovery*
  • Drug Synergism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Proteins / antagonists & inhibitors
  • Proteins / metabolism
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism
  • Triazoles / chemistry
  • Triazoles / metabolism
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism


  • (+)-JQ1 compound
  • Antineoplastic Agents
  • Azepines
  • BRD4 protein, human
  • Cell Cycle Proteins
  • Nuclear Proteins
  • Proteins
  • Transcription Factors
  • Triazoles
  • bromodomain and extra-terminal domain protein, human
  • Ubiquitin-Protein Ligases

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