Recent Advances in Dual BRD4‐Kinase Inhibitors Based on Polypharmacology

The epigenetic reader BRD4 is involved in chromatin remodelling and transcriptional regulation, making it a promising therapeutic target. However, over the past decades, many BRD4 inhibitors that entered clinical trials were, in the main, unsatisfactory, due to some therapeutic limitations such as off‐target effects and drug resistance. Combining a BRD4 inhibitor with another drug was expected to be an ideal option to overcome these hurdles and to improve therapeutic outcomes. However, such combination therapy could trigger toxicity caused by drug‐drug interactions, complex pharmacokinetics, and additive effects. Recently, the application of dual‐target drugs targeting BRD4 and other kinases has become an attractive approach to remedy the defects of a single BRD4 inhibitor. This review focuses on recent advances in the discovery of dual BRD4‐kinase inhibitors, with an emphasis on their co‐crystal structures and structure‐activity relationships (SARs), as well as future perspectives in this field.

• Publication year

  2022

• Venue

  ChemMedChem

• Publication date

  2022-02-11

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/cmdc.202100731PMID 35146935
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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