Abstract
Regulation of gene expression is mediated by several mechanisms such as DNA methylation, ATP-dependent chromatin remodeling, and post-translational modifications of histones. The latter mechanism includes dynamic acetylation and deacetylation of η- amino groups of lysine residues present in the tail of the core histones. Enzymes responsible for the reversible acetylation/deacetylation processes are histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. There are three mammalian HDAC families, namely HDACs I, II and III based on their sequence homology. Inhibitors of HDACs induce hyperacetylation of histones that modulate chromatin structure and gene expression resulting in growth arrest, cell differentiation, and apoptosis of tumor cells. In addition, HDAC inhibitors enhance efficacy of anticancer agents that target DNA. Several formidable challenges associated with their development include non-specific toxicity and poor PK properties, including cell permeability. In this review, we comment on the current progress in design, discovery, in vitro/ex vivo activity and clinical potential of the synthetic modulators of HDACs.
Keywords: HDAC, Histone, inhibitors, cancer, QSAR, pharmacophore, docking, bioisoster
Anti-Cancer Agents in Medicinal Chemistry
Title: Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective
Volume: 7 Issue: 5
Author(s): Konstantin V. Balakin, Yan A. Ivanenkov, Alex S. Kiselyov and Sergey E. Tkachenko
Affiliation:
Keywords: HDAC, Histone, inhibitors, cancer, QSAR, pharmacophore, docking, bioisoster
Abstract: Regulation of gene expression is mediated by several mechanisms such as DNA methylation, ATP-dependent chromatin remodeling, and post-translational modifications of histones. The latter mechanism includes dynamic acetylation and deacetylation of η- amino groups of lysine residues present in the tail of the core histones. Enzymes responsible for the reversible acetylation/deacetylation processes are histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. There are three mammalian HDAC families, namely HDACs I, II and III based on their sequence homology. Inhibitors of HDACs induce hyperacetylation of histones that modulate chromatin structure and gene expression resulting in growth arrest, cell differentiation, and apoptosis of tumor cells. In addition, HDAC inhibitors enhance efficacy of anticancer agents that target DNA. Several formidable challenges associated with their development include non-specific toxicity and poor PK properties, including cell permeability. In this review, we comment on the current progress in design, discovery, in vitro/ex vivo activity and clinical potential of the synthetic modulators of HDACs.
Export Options
About this article
Cite this article as:
Balakin V. Konstantin, Ivanenkov A. Yan, Kiselyov S. Alex and Tkachenko E. Sergey, Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (5) . https://dx.doi.org/10.2174/187152007781668698
DOI https://dx.doi.org/10.2174/187152007781668698 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
A Computational Study of Three Frequent Mutations of EGFR and their Effects on Protein Dimer Formation and Non-Small Cell Lung Cancer Drug Resistance
Current Bioinformatics Smac-Derived Aza-Peptide As an Aminopeptidase-Resistant XIAP BIR3 Antagonist
Protein & Peptide Letters Pleiotropic Role of HSF1 in Neoplastic Transformation
Current Cancer Drug Targets New Agents – Manifold Consequences: The Management of Lung and Colorectal Cancer is Changing
Current Cancer Therapy Reviews MicroRNAs: Potential Diagnostic and Therapeutic Targets for Breast Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Prediction and Early Evaluation of Anticancer Therapy Response: From Imaging of Drug Efflux Pumps to Targeted Therapy Response
Current Medicinal Chemistry Preparation, Characterization, and In Vitro Release of Vinorelbine Tartrate (VLBT)- Loaded Folate-conjugated Recombination Human Serum Albumin (rHSA) Nanoparticles with Different Degree of Cross-linking
Current Nanoscience Cow’s Milk Allergy in Children, from Avoidance to Tolerance
Endocrine, Metabolic & Immune Disorders - Drug Targets Mechanisms of Intrinsic and Acquired Resistance to EGFR Inhibitors
Current Cancer Therapy Reviews Drug Repurposing in Chemical Genomics: Can We Learn from the Past to Improve the Future?
Current Topics in Medicinal Chemistry New Perspectives Regarding Anaplastic Thyroid Carcinoma Approach Improvement
Endocrine, Metabolic & Immune Disorders - Drug Targets Crystal Structures of Acridines Complexed with Nucleic Acids
Medicinal Chemistry Reviews - Online (Discontinued) Polyoxometalates in Biomedicine: Update and Overview
Current Medicinal Chemistry New Horizons in the Etiopathogenesis and Non-Invasive Diagnosis of Endometriosis.
Current Molecular Medicine Selective Modulation of Aβ42 Production in Alzheimers Disease: Non-Steroidal Anti-Inflammatory Drugs and Beyond
Current Pharmaceutical Design Acute Kidney Injury: Turning the Tide
Current Drug Targets <sup>18</sup>F-DOPA and <sup>18</sup>F-FDG PET/CT, Scintigraphic Localization and Radioguided Surgery of Recurrent Medullary Thyroid Cancer: Two Case Reports
Current Radiopharmaceuticals Severe Hypoglycemia Due to Possible Interaction Between Glibenclamide and Sorafenib in a Patient with Hepatocellular Carcinoma
Current Drug Safety Dual Roles of Sulforaphane in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Talin: A Potential Drug Target for Cancer Therapy
Current Drug Metabolism