Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Drug Discov Today. 2022 Jan;27(1):246-256. doi: 10.1016/j.drudis.2021.08.007. Epub 2021 Aug 23.

Abstract

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein-protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.

Keywords: Bromodomain-containing protein 4 (BRD4); Cancer therapy; Designing strategy; Dual-target inhibitor; Small-molecule drug.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Proteins* / antagonists & inhibitors
  • Cell Cycle Proteins* / metabolism
  • Drug Design / methods*
  • Humans
  • Molecular Targeted Therapy* / methods
  • Molecular Targeted Therapy* / trends
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Structure-Activity Relationship
  • Transcription Factors* / antagonists & inhibitors
  • Transcription Factors* / metabolism

Substances

  • Antineoplastic Agents
  • BRD4 protein, human
  • Cell Cycle Proteins
  • Transcription Factors