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
-
Cytotoxic and Allergenic Potential of Bioactive Proteins and Peptides
Current Pharmaceutical Design Progress in Multiple Sclerosis Genetics
Current Genomics Brain Tumour Stem Cells: Implications for Cancer Therapy and Regenerative Medicine
Current Stem Cell Research & Therapy Natural Product Inhibitors of the Ubiquitin-Proteasome Pathway
Current Drug Targets Growth and Trophic Factors, pH and the Na+/H+ Exchanger in Alzheimers Disease, Other Neurodegenerative Diseases and Cancer: New Therapeutic Possibilities and Potential Dangers
Current Alzheimer Research Nilotinib Therapy in Chronic Myelogenous Leukemia: The Strength of High Selectivity on BCR/ABL
Current Drug Targets Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New Selective Molecules to Hematopoietic Neoplastic Cells
Combinatorial Chemistry & High Throughput Screening Histone Deacetylase Inhibitors and Neurodegenerative Disorders: Holding the Promise
Current Pharmaceutical Design B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry Targeting Histone Onco- Modifications Using Plant-Derived Products
Current Drug Targets The Prevention of Oral Mucositis in Patients with Blood Cancers: Current Concepts and Emerging Landscapes
Cardiovascular & Hematological Agents in Medicinal Chemistry Fragment-Based Optimization of Small Molecule CXCL12 Inhibitors for Antagonizing the CXCL12/CXCR4 Interaction
Current Topics in Medicinal Chemistry The MYC Oncogene as a Cancer Drug Target
Current Cancer Drug Targets Sequence and Structural Elements in the Mechanism of Function of Rhodopsin-Like Family of G Protein-Coupled-Receptors
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Recent Progress of Small Molecular VEGFR Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry 3D-QSAR and Docking Studies on 2-acyliminobenzimidazoles Derivatives as Potent ALK Inhibitors
Letters in Drug Design & Discovery Chemical Origins of Isoform Selectivity in Histone Deacetylase Inhibitors
Current Pharmaceutical Design Disease Progression in HIV Late Presenters: the Role of HIV Clinical Indicator Diseases Prior to HIV Diagnosis
Current HIV Research Integrins as Novel Drug Targets for Overcoming Innate Drug Resistance
Current Cancer Drug Targets Clinical Applicability of Microarray Technology in the Diagnosis, Prognostic Stratification, Treatment and Clinical Surveillance of Cervical Adenocarcinoma
Current Pharmaceutical Design