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Updated: Jul 4, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Isoform-selective histone deacetylase inhibitors
Anton V Bieliauskas1, Mary Kay H Pflum
1Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Abstract:
Histone deacetylase (HDAC) proteins are transcription regulators linked to cancer. As a result, multiple small molecule HDAC inhibitors are in various phases of clinical trials as anti-cancer drugs. The majority of HDAC inhibitors non-selectively influence the activities of eleven human HDAC isoforms, which are divided into distinct classes. This tutorial review focuses on the recent progress toward the identification of class-selective and isoform-selective HDAC inhibitors. The emerging trends suggest that subtle differences in the active sites of the HDAC isoforms can be exploited to dictate selectivity.
Insights
Developing selective histone deacetylase (HDAC) inhibitors is crucial for cancer therapy. This review highlights progress in creating HDAC inhibitors that target specific HDAC classes and isoforms, exploiting active site differences for better drug design.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Histone deacetylase (HDAC) proteins are key regulators of gene transcription and are implicated in various cancers.
- Numerous small molecule HDAC inhibitors are under investigation as anti-cancer therapeutics, with many in clinical trials.
- Current HDAC inhibitors often lack selectivity, affecting multiple HDAC isoforms across different classes.
Purpose of the Study:
- To review recent advancements in the development of class-selective and isoform-selective HDAC inhibitors.
- To explore strategies for achieving selectivity based on structural differences in HDAC active sites.
- To provide insights into emerging trends in targeted HDAC inhibition for cancer treatment.
Main Methods:
- Literature review of recent research on HDAC inhibitor development.
- Analysis of studies focusing on structure-activity relationships for HDAC isoform selectivity.
- Discussion of emerging trends and future directions in targeted HDAC inhibition.
Main Results:
- Significant progress has been made in identifying HDAC inhibitors with improved class and isoform selectivity.
- Subtle differences within the active sites of HDAC isoforms present opportunities for designing targeted inhibitors.
- Emerging trends indicate a shift towards precision medicine approaches in HDAC inhibitor development.
Conclusions:
- Targeted inhibition of specific HDAC isoforms holds promise for more effective and less toxic cancer therapies.
- Exploiting active site variations is a key strategy for achieving desired selectivity in HDAC inhibitor design.
- Continued research in this area is essential for advancing the clinical application of HDAC inhibitors in oncology.
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