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BET Bromodomain Inhibitors as an Emerging Class of Anticancer Agents

A Review of Drug Discovery, Strategy, and Tactics

  • Living reference work entry
  • First Online:
Handbook of Cancer and Immunology

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Abstract

Deregulated gene expression including epigenetic modulation is considered one of the most prominent factors that leads to tumorigenesis, thus nominating transcriptional regulators as potential therapeutic targets. Among these epigenetic regulators is a family of evolutionarily conserved motifs known as bromodomains (BRDs), which can be further subcategorized into extraterminal BRDs (BET) or non-BET BRDs. Functionally, BRDs belong to epigenetic readers that bind to acetylated lysine residues on the histone tails and then act as transcriptional coactivators via the recruitment of partner transcriptional factors to the activation sites of target genes. Moreover, BRDs are known for their structural complexity endowed by their varied regulations based on their isoforms, expression pattern, and functionality within diverse tumor types. Provided the prominence of their biological activity and the fact that they get deregulated in different tumor types, growing research efforts are increasingly devoted for develo** small molecules targeting them. Intriguingly, BRD inhibitors were reported to suppress the transcription of oncogenes at doses that are well-tolerated by normal tissue, a property that promoted their progress in clinical testing. In this review, we will highlight the structural diversity among the different classes of BET inhibitors along with their molecular targets. Special focus will be lent to BRD4 along with shedding light on the potential attributes leading to therapeutic selectivity of its inhibitors. This collective review paves the way for better understanding of the SAR of BET inhibitors to expectantly expedite advances in development of new inhibitors possessing optimum affinity and selectivity.

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Authors Contribution Statement

All authors have participated to the conception and design of the work; have drafted the work and revised it. All authors have approved the submitted version and have agreed to be personally accountable for their contribution.

Competing Interests Statement

The authors declare no competing interests.

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Authors and Affiliations

  1. Drug Design and Discovery Laboratory, Helmy Institute of Medical Sciences, Zewail City of Science, Technology and Innovation, Cairo, Egypt

    Ragaa Yasser, Nada K. Sedky & Reem K. Arafa

  2. Biomedical Sciences Program, University of Science, Technology and Innovation, Zewail City of Science and Technology, Cairo, Egypt

    Ragaa Yasser & Reem K. Arafa

  3. NanoScience Program, University of Science and Technology, Zewail City of Science and Technology, Cairo, Egypt

    Kholoud K. Arafa

  4. Department of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt

    Nada K. Sedky

  5. Department of Biochemistry, Faculty of Pharmacy, Sinai University, Cairo, Egypt

    Kirullos R. Sidaros

Authors
  1. Ragaa Yasser
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  2. Kholoud K. Arafa
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  3. Nada K. Sedky
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  4. Kirullos R. Sidaros
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  5. Reem K. Arafa
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Corresponding author

Correspondence to Reem K. Arafa .

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Editors and Affiliations

  1. Division of Clinical Immunology, Karolinska University Hospital, Huddinge, Sweden

    Nima Rezaei

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Yasser, R., Arafa, K.K., Sedky, N.K., Sidaros, K.R., Arafa, R.K. (2024). BET Bromodomain Inhibitors as an Emerging Class of Anticancer Agents. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_401-1

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  • DOI: https://doi.org/10.1007/978-3-030-80962-1_401-1

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  • Print ISBN: 978-3-030-80962-1

  • Online ISBN: 978-3-030-80962-1

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