Abstract
Trichostatin A (TSA) is a Streptomyces metabolite that causes differentiation of murine erythroleukemia cells as well as specific inhibition of the cell cycle of some lower eukaryotes and mammalian cells. The targeted molecule of TSA has been shown by genetic and biochemical analyses to be histone deacetylases (HDACs). Histone acetylation is a key modification to control transcription, and HDACs are profoundly involved in pathogenesis of cancer through removing acetyl groups from histones and other transcriptional regulators. Trapoxin (TPX) and FK228 (also known as FR901228 and depsipeptide because FK228 = FR901228 = depsipeptide), structurally unrelated microbial metabolites, were also shown to inhibit HDACs. These HDAC inhibitors cause cell cycle arrest, differentiation and / or apoptosis of many tumors, suggesting their usefulness for chemotherapy and differentiation therapy. In addition, HDAC inhibitors play important roles in identifying the specific function of the enzymes. Indeed, we identified tubulin as one of the substrates of HDAC6 by means of differential sensitivity to HDAC inhibitors. Since recent studies have revealed that HDACs are structurally and functionally diverse, it should be important to develop inhibitors specific to individual enzymes as more promising agents for cancer therapy. We have synthesized novel TSA / TPX hybrids, which will serve as a basis for developing enzyme-specific HDAC inhibitors.
Keywords: acetylation, anticancer, chap, chromatin, transcription, trapoxin, trichostatin
Current Medicinal Chemistry
Title: From Discovery to the Coming Generation of Histone Deacetylase Inhibitors
Volume: 10 Issue: 22
Author(s): Minoru Yoshida, Akihisa Matsuyama, Yasuhiko Komatsu and Norikazu Nishino
Affiliation:
Keywords: acetylation, anticancer, chap, chromatin, transcription, trapoxin, trichostatin
Abstract: Trichostatin A (TSA) is a Streptomyces metabolite that causes differentiation of murine erythroleukemia cells as well as specific inhibition of the cell cycle of some lower eukaryotes and mammalian cells. The targeted molecule of TSA has been shown by genetic and biochemical analyses to be histone deacetylases (HDACs). Histone acetylation is a key modification to control transcription, and HDACs are profoundly involved in pathogenesis of cancer through removing acetyl groups from histones and other transcriptional regulators. Trapoxin (TPX) and FK228 (also known as FR901228 and depsipeptide because FK228 = FR901228 = depsipeptide), structurally unrelated microbial metabolites, were also shown to inhibit HDACs. These HDAC inhibitors cause cell cycle arrest, differentiation and / or apoptosis of many tumors, suggesting their usefulness for chemotherapy and differentiation therapy. In addition, HDAC inhibitors play important roles in identifying the specific function of the enzymes. Indeed, we identified tubulin as one of the substrates of HDAC6 by means of differential sensitivity to HDAC inhibitors. Since recent studies have revealed that HDACs are structurally and functionally diverse, it should be important to develop inhibitors specific to individual enzymes as more promising agents for cancer therapy. We have synthesized novel TSA / TPX hybrids, which will serve as a basis for developing enzyme-specific HDAC inhibitors.
Export Options
About this article
Cite this article as:
Yoshida Minoru, Matsuyama Akihisa, Komatsu Yasuhiko and Nishino Norikazu, From Discovery to the Coming Generation of Histone Deacetylase Inhibitors, Current Medicinal Chemistry 2003; 10 (22) . https://dx.doi.org/10.2174/0929867033456602
DOI https://dx.doi.org/10.2174/0929867033456602 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![](/images/wayfinder.jpg)
- 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
-
Piperine from Black Pepper Decreased the Expression of Intercellular Adhesion Molecule-1 in Macrophages
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Brain Permeable Nanoparticles
Recent Patents on CNS Drug Discovery (Discontinued) Pathophysiology of Erectile Dysfunction
Current Drug Targets Yoga can Alter the Autonomic Neural Activity: A Critical Analysis
Current Traditional Medicine Subject Index to Volume 1
Current Neurovascular Research Subject Index to Volume 4
Current Topics in Medicinal Chemistry Activators and Inhibitors of the Ion Channel of the NMDA Receptor
Current Drug Targets Advanced Platelet-Rich Fibrin Extract Treatment Promotes the Proliferation and Differentiation of Human Adipose-Derived Mesenchymal Stem Cells through Activation of Tryptophan Metabolism
Current Stem Cell Research & Therapy Editorial
Current Drug Safety Targeting Potassium Channels: New Advances in Cardiovascular Therapy
Recent Patents on Cardiovascular Drug Discovery Integrating Virtual Screening Methods to the Quest for Novel Membrane Protein Ligands
Current Medicinal Chemistry - Central Nervous System Agents Antiepileptic Drug Monotherapy: The Initial Approach in Epilepsy Management
Current Neuropharmacology Cognitive Impairment and Mossy Fiber Sprouting in a Rat Model of Drug-resistant Epilepsy Induced by Lithium-pilocarpine
Current Neurovascular Research Studies on Target Genes of General Anesthetics-Version 2
Medicinal Chemistry Reviews - Online (Discontinued) Valproate Induced Acute Pancreatitis - A Unique Case Report
Current Drug Safety T-type Calcium Channels in Health and Disease
Current Medicinal Chemistry Identification of Molecular Targets Associated with Ethanol Toxicity and Implications in Drug Development
Current Pharmaceutical Design Structure-Activity Relationships of Selective GABA Uptake Inhibitors
Current Topics in Medicinal Chemistry Nitric Oxide, Peroxynitrite, Peroxynitrous Acid, Nitroxyl, Nitrogen Dioxide, Nitrous Oxide: Biochemical Mechanisms and Bioaction
Current Bioactive Compounds Interactions between Ketamine and Magnesium for the Treatment of Pain: Current State of the Art
CNS & Neurological Disorders - Drug Targets