Abstract
The dynamics of gene expression are regulated by histone acetylases (HATs) and histone deacetylases (HDACs) that control the acetylation state of lysine side chains of the histone proteins of chromatin. The catalytic activity of these two enzymes remodels chromatin to control gene expression without altering gene sequence. Treatment of cancer has been the primary target for the clinical development of HDAC inhibitors, culminating in approval for the first HDAC inhibitor for the treatment of cutaneous T cell lymphoma. Beyond cancer, HDAC inhibition has potential for the treatment of many other diseases. The HDAC inhibitors phenylbutyric acid, valproic acid, and suberoylanilide hydroxamic acid (SAHA) have been shown to correct errant gene expression, ameliorate the progression of disease, and restore absent synthetic or metabolic activities for a diverse group of non-cancer disorders. These benefits have been found in patients with sickle cell anemia, HIV, and cystic fibrosis. In vitro and in vivo models of spinal muscular atrophy, muscular dystrophy, and neurodegenerative, and inflammatory disorders also show response to HDAC inhibitors. This review examines the application of HDAC inhibition as a treatment for a wide-range of non-cancer disorders, many of which are rare diseases that urgently need therapy. Inhibition of the HDACs has general potential as a pharmacological epigenetic approach for gene therapy.
Current Topics in Medicinal Chemistry
Title: Inhibition of Histone Deacetylases: A Pharmacological Approach to the Treatment of Non-Cancer Disorders
Volume: 9 Issue: 3
Author(s): Norbert L. Wiech, Jed F. Fisher, Paul Helquist and Olaf Wiest
Affiliation:
Abstract: The dynamics of gene expression are regulated by histone acetylases (HATs) and histone deacetylases (HDACs) that control the acetylation state of lysine side chains of the histone proteins of chromatin. The catalytic activity of these two enzymes remodels chromatin to control gene expression without altering gene sequence. Treatment of cancer has been the primary target for the clinical development of HDAC inhibitors, culminating in approval for the first HDAC inhibitor for the treatment of cutaneous T cell lymphoma. Beyond cancer, HDAC inhibition has potential for the treatment of many other diseases. The HDAC inhibitors phenylbutyric acid, valproic acid, and suberoylanilide hydroxamic acid (SAHA) have been shown to correct errant gene expression, ameliorate the progression of disease, and restore absent synthetic or metabolic activities for a diverse group of non-cancer disorders. These benefits have been found in patients with sickle cell anemia, HIV, and cystic fibrosis. In vitro and in vivo models of spinal muscular atrophy, muscular dystrophy, and neurodegenerative, and inflammatory disorders also show response to HDAC inhibitors. This review examines the application of HDAC inhibition as a treatment for a wide-range of non-cancer disorders, many of which are rare diseases that urgently need therapy. Inhibition of the HDACs has general potential as a pharmacological epigenetic approach for gene therapy.
Export Options
About this article
Cite this article as:
Wiech L. Norbert, Fisher F. Jed, Helquist Paul and Wiest Olaf, Inhibition of Histone Deacetylases: A Pharmacological Approach to the Treatment of Non-Cancer Disorders, Current Topics in Medicinal Chemistry 2009; 9 (3) . https://dx.doi.org/10.2174/156802609788085241
DOI https://dx.doi.org/10.2174/156802609788085241 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Kinases as Drug Discovery Targets in Hematologic Malignancies
Current Molecular Medicine Light Alcohol Drinking and the Risk of Cancer Development: A Controversial Relationship
Reviews on Recent Clinical Trials Emerging Strategies to Strengthen the Anti-Tumour Activity of Type I Interferons: Overcoming Survival Pathways
Current Cancer Drug Targets STAT 3 as a Target for Cancer Drug Discovery
Current Medicinal Chemistry Drug Combinations Enhancing the Antineoplastic Effects of Erlotinib in High-Grade Glioma
Recent Patents on Anti-Cancer Drug Discovery Multiple Myeloma and the Immune Microenvironment
Current Cancer Drug Targets Recent Advances in Oncogenic Roles of the TRPM7 Chanzyme
Current Medicinal Chemistry Impact of Cellular Senescence in Aging and Cancer
Current Pharmaceutical Design Discovery of Novel HDAC Inhibitors by Structure-based Optimization of Cinnamic Hydroxamic Scaffold
Letters in Drug Design & Discovery CDC25 Phosphatase Inhibitors: An Update
Mini-Reviews in Medicinal Chemistry Antisense Therapy for Cardiovascular Diseases
Current Pharmaceutical Design Biosurfactants as a Novel Additive in Pharmaceutical Formulations: Current Trends and Future Implications
Current Drug Metabolism Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients
Current Pharmacogenomics and Personalized Medicine Survey of Computational Algorithms for MicroRNA Target Prediction
Current Genomics The CXCL12/CXCR4 Axis as a Therapeutic Target in Cancer and HIV-1 Infection
Current Medicinal Chemistry Mouse Models of Primary Sjogren’s Syndrome
Current Pharmaceutical Design How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization
Mini-Reviews in Medicinal Chemistry Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation
Current HIV Research Organ- and Cell-Type Specific Delivery of Kinase Inhibitors: A Novel Approach in the Development of Targeted Drugs
Current Molecular Pharmacology Antiviral Drugs in the Prophylaxis of HBV Infection
Current Medicinal Chemistry