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 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- 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
-
Exploiting Apoptosis Pathways for the Treatment of Pancreatic Cancer
Current Signal Transduction Therapy Approaches to Targeting Cancer Stem Cells in Solid Tumors
Current Stem Cell Research & Therapy An Emerging Strategy for Cancer Treatment Targeting Aberrant Glycogen Synthase Kinase 3β
Anti-Cancer Agents in Medicinal Chemistry Manipulation of Glycolysis in Malignant Tumors: Fantasy or Therapy?
Current Medicinal Chemistry Antioxidant Effect of Mangiferin and its Potential to be a Cancer Chemoprevention Agent
Letters in Drug Design & Discovery TGF-β and Hepatocellular Carcinoma: When A Friend Becomes An Enemy
Current Protein & Peptide Science Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery
Current Pharmaceutical Design Can EGFR-Tyrosine Kinase Inhibitors (TKI) Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion (MPE) in Lung Adenocarcinoma
Current Drug Discovery Technologies Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias
Current Pharmaceutical Design New Drug Targets for Genomic Cancer Therapy Successes, Limitations, Opportunities and Future Challenges
Current Cancer Drug Targets Novel Series of Coumarinyl Substituted-thiazolidin-2,4-dione Analogs as Anticancer Agents: Design, Synthesis, Spectral Studies and Cytotoxicity Evaluation
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Traditional Medicine Zoledronic Acid Inhibits the RhoA-mediated Amoeboid Motility of Prostate Cancer Cells
Current Cancer Drug Targets Retroviral Gene Therapy: Safety Issues and Possible Solutions
Current Gene Therapy Editorial [Hot topic: New Generation Cancer Vaccines: From Tumor Immunology to Clinical Applications (Executive Editor: Simone Mocellin)]
Current Pharmaceutical Design Zebrafish As a Genetic Model in Pre-Clinical Drug Testing and Screening
Current Medicinal Chemistry An Integrated Chikungunya Virus Database to Facilitate Therapeutic Analysis: ChkVDb
Current Bioinformatics Angiogenesis Inhibition in the Treatment of Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry A New Synthesis for Acacetin, Chrysoeriol, Diosmetin, Tricin and Other Hydroxylated Flavones by Modified Baker-Venkataraman Transformation
Letters in Organic Chemistry Designed Multiple Ligands: Basic Research vs Clinical Outcomes
Current Medicinal Chemistry