Abstract
Histone deacetylase (HDAC) enzymes have emerged as promising targets for the treatment of a wide range of human diseases, including cancers, inflammatory and metabolic disorders, immunological, cardiovascular, and infectious diseases. At present, such applications are limited by the lack of selective inhibitors available for each of the eighteen HDAC enzymes, with most currently available HDAC inhibitors having broad-spectrum activity against multiple HDAC enzymes. Such broad-spectrum activity maybe useful in treating some diseases like cancers, but can be detrimental due to cytotoxic side effects that accompany prolonged treatment of chronic diseased states. Here we summarize progress towards the design and discovery of HDAC inhibitors that are selective for some of the eleven zinc-containing classical HDAC enzymes, and identify opportunities to use such isozyme-selective inhibitors as chemical probes for interrogating the biological roles of individual HDAC enzymes in diseases.
Keywords: Histone deacetylase, HDAC inhibitor, isoform, isozyme, cancer, inflammation, metabolic, promising targets, immunological, cardiovascular, cytotoxic, lysine residues, cellular proteins, phosphorylation, small molecule chemical inhibitors, therapeutic drugs
Current Topics in Medicinal Chemistry
Title:Towards Isozyme-Selective HDAC Inhibitors For Interrogating Disease
Volume: 12 Issue: 14
Author(s): Praveer Gupta, Robert C. Reid, Abishek Iyer, Matthew J. Sweet and David P. Fairlie
Affiliation:
Keywords: Histone deacetylase, HDAC inhibitor, isoform, isozyme, cancer, inflammation, metabolic, promising targets, immunological, cardiovascular, cytotoxic, lysine residues, cellular proteins, phosphorylation, small molecule chemical inhibitors, therapeutic drugs
Abstract: Histone deacetylase (HDAC) enzymes have emerged as promising targets for the treatment of a wide range of human diseases, including cancers, inflammatory and metabolic disorders, immunological, cardiovascular, and infectious diseases. At present, such applications are limited by the lack of selective inhibitors available for each of the eighteen HDAC enzymes, with most currently available HDAC inhibitors having broad-spectrum activity against multiple HDAC enzymes. Such broad-spectrum activity maybe useful in treating some diseases like cancers, but can be detrimental due to cytotoxic side effects that accompany prolonged treatment of chronic diseased states. Here we summarize progress towards the design and discovery of HDAC inhibitors that are selective for some of the eleven zinc-containing classical HDAC enzymes, and identify opportunities to use such isozyme-selective inhibitors as chemical probes for interrogating the biological roles of individual HDAC enzymes in diseases.
Export Options
About this article
Cite this article as:
Gupta Praveer, C. Reid Robert, Iyer Abishek, J. Sweet Matthew and P. Fairlie David, Towards Isozyme-Selective HDAC Inhibitors For Interrogating Disease, Current Topics in Medicinal Chemistry 2012; 12 (14) . https://dx.doi.org/10.2174/156802612802652420
DOI https://dx.doi.org/10.2174/156802612802652420 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
The Role of Colchicine in Pericardial Syndromes
Current Pharmaceutical Design PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration
Current Alzheimer Research Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Protein Aggregation and Self Assembly in Health and Disease
Current Proteomics Imidazoline Receptor Agonists in Obesity-Related Hypertension: Therapeutic Targeting of the Sympathetic Nervous System
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Targeted-liposome Delivery System of Antitumor Drugs
Current Drug Metabolism Can PPARγ Ligands Be Used in Cancer Therapy?
Current Medicinal Chemistry - Anti-Cancer Agents ADAM17 as a Therapeutic Target in Multiple Diseases
Current Pharmaceutical Design Sarcopenia, Cachexia and Congestive Heart Failure in the Elderly
Endocrine, Metabolic & Immune Disorders - Drug Targets Integrin α4β7 Antagonists: Activities, Mechanisms of Action and Therapeutic Prospects
Current Immunology Reviews (Discontinued) Hypertension - Current Natural Strategies to Lower Blood Pressure
Current Pharmaceutical Design Endothelial Dysfunction in Morbid Obesity
Current Pharmaceutical Design Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology
Combinatorial Chemistry & High Throughput Screening The Involvement of Lysosomes in Myocardial Aging and Disease
Current Cardiology Reviews Expression and Functions of Vasoactive Substances Regulated by Hypoxia-Inducible Factor-1 in Chronic Hypoxemia
Cardiovascular & Hematological Agents in Medicinal Chemistry The Chick Embryo Chorioallantoic Membrane as a Model for in vivo Research on Anti-Angiogenesis
Current Pharmaceutical Biotechnology Dissecting abdominal aortic aneurysm in Angiotensin II-infused mice: the importance of imaging
Current Pharmaceutical Design Tissue Doppler Imaging: Beautiful Noise
Current Cardiology Reviews Lipids and Lysosomes
Current Drug Metabolism Regressing Left Ventricular Hypertrophy: The Role of Telmisartan and Other ARBs
Current Hypertension Reviews