Related Experiment Video
Updated: May 9, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery
Jun-Jie Wang1, Ya Gao1, Xin-Qian Ji1
1State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of Henan Province for Small Molecule Drug Discovery and Application, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Medicinal Research Reviews
|May 8, 2026
Summary
Proteolysis-targeting chimeras (PROTACs) offer a novel approach to degrade histone deacetylases (HDACs), overcoming limitations of traditional inhibitors for cancer therapy.
Area of Science:
- Epigenetics and Molecular Biology
- Cancer Therapeutics
- Drug Discovery
Background:
- Histone deacetylases (HDACs) are crucial epigenetic regulators implicated in various cancers.
- Current HDAC inhibitors face challenges including limited isoform selectivity, resistance, and toxicity.
- Proteolysis-targeting chimeras (PROTACs) offer a new strategy for targeted protein degradation.
Purpose of the Study:
- To review the structural and functional aspects of HDACs.
- To survey recent advancements in the design of HDAC-targeted PROTACs.
- To discuss the potential of HDAC degraders in cancer treatment.
Main Methods:
- Review of structural classification and biological functions of HDACs.
- Survey of recent literature on HDAC-directed PROTAC design.
- Evaluation of pharmacological characteristics and antitumor efficacy of representative HDAC degraders.
Main Results:
- PROTACs enable targeted ubiquitin-proteasome-mediated degradation of HDACs.
- This approach enhances specificity and overcomes resistance mechanisms.
- HDAC degraders demonstrate sustained suppression and antitumor efficacy.
Conclusions:
- HDAC-directed PROTACs represent a promising therapeutic strategy for cancer.
- Rational design involving warhead, linker, and E3 ligase selection is key.
- Further development is needed to translate HDAC degraders into clinical applications.
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