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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
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HDAC8 as a target in drug discovery: Function, structure and design.

Qianlong Zhao1, Hongyan Liu2, Jie Peng1

  • 1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China.

European Journal of Medicinal Chemistry
|October 20, 2024
PubMed
Summary

Histone deacetylase 8 (HDAC8) is a key target for drug discovery, involved in diverse biological processes and diseases. Novel strategies like innovative zinc-chelating groups and PROTACs are advancing HDAC8 inhibitor development for potential clinical use.

Keywords:
CancerHDAC8HDAC8 inhibitorHistone deacetylaseInhibitor designPROTAC

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Histone deacetylases (HDACs) are crucial therapeutic targets.
  • HDAC8, a Class I HDAC, has unique structural and physiological properties.
  • HDAC8 deacetylates numerous non-histone substrates, impacting diverse biological pathways.

Purpose of the Study:

  • To review recent advancements in HDAC8 inhibitor development.
  • To highlight novel strategies for targeting HDAC8.
  • To provide an overview of clinical progress for HDAC8 inhibitors.

Main Methods:

  • Literature review of recent studies on HDAC8 inhibitors.
  • Analysis of novel targeting strategies, including zinc-chelating groups and PROTACs.
  • Summary of clinical advancements and challenges.

Main Results:

  • HDAC8 plays significant roles in diseases like AML and neuroblastoma.
  • Several HDAC8 inhibitors have been developed, but only one reached clinical trials.
  • Emerging strategies focus on innovative zinc-chelating groups, multi-target drugs, and HDAC8 PROTACs.

Conclusions:

  • HDAC8 is a promising target for treating various diseases.
  • Novel strategies are crucial for developing effective HDAC8 inhibitors.
  • Further research and clinical studies are needed to translate these advancements into therapies.