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
-
Epigenetic MicroRNA Regulation of Multiple Chromatin Functions: A Perspective in Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Immunomodulatory Role of Arsenic in Regulatory T Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting Aurora Kinases in Cancer Treatment
Current Drug Targets Nicotinamide Adenine Dinucleotide Based Therapeutics
Current Medicinal Chemistry Biologics: An Update and Challenge of Their Pharmacokinetics
Current Drug Metabolism Targeting ATP7A to Increase the Sensitivity of Neuroblastoma Cells to Retinoid Therapy
Current Cancer Drug Targets Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment
Current Cancer Drug Targets Hereditary Breast Cancer in Sub-Saharan Africa
Current Women`s Health Reviews In Vitro Intestinal Co-Culture Cell Model to Evaluate Intestinal Absorption of Edelfosine Lipid Nanoparticles
Current Topics in Medicinal Chemistry Male Fertility-Implications of Anticancer Treatment and Strategies to Mitigate Gonadotoxicity
Anti-Cancer Agents in Medicinal Chemistry HDACs and HDAC Inhibitors in Urothelial Carcinoma – Perspectives for an Antineoplastic Treatment
Current Medicinal Chemistry Raman Spectroscopy and Imaging: Promising Optical Diagnostic Tools in Pediatrics
Current Medicinal Chemistry Lymphoproliferative Lesions in IgG4-Related Disease
Current Immunology Reviews (Discontinued) Radionuclide Antibody-Conjugates, a Targeted Therapy Towards Cancer
Current Radiopharmaceuticals Targeting the Nucleus: An Overview of Auger-Electron Radionuclide Therapy
Current Drug Discovery Technologies Nuclear PI-PLCβ1 and Myelodysplastic Syndromes: Genetics and Epigenetics
Current Pharmaceutical Design Cadherins: The Superfamily Critically Involved in Breast Cancer
Current Pharmaceutical Design Lipid Nucleoside Conjugates for the Treatment of Cancer
Current Pharmaceutical Design Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies
Recent Patents on Anti-Cancer Drug Discovery Neuroimaging of Non-Accidental Injury
Current Pediatric Reviews