Abstract
A better understanding of the biological roles and the pathological consequences of thiol-dependent enzymes has emerged in recent years, and hence considerable progress has been made in identifying and delineating cysteine proteases that can be considered promising drug targets from those involved in housekeeping functions. Cysteine proteases have been implicated in a wide variety of disease processes ranging from cardiovascular, inflammatory, viral and immunological disorders to cancer. The first milestone in drug development of cysteine protease inhibitors has probably been reached, as IDN-6556 (a broad spectrum caspase inhibitor) has recently received Orphan Drug label by the U.S. Food and Drug Administration for use in the treatment of the patients undergoing liver transplantation and other solid organ transplantation. IDN-6556, which blocks apoptosis, is in Phase II human clinical trial in patients undergoing liver transplantation. In addition, more than ten cysteine protease inhibitors are presently at various phases of clinical development/trials for diverse diseases. This review emphasises on the new development from the literature reports since the year 2000 in the exploration of potential cysteine proteases as prospective drug targets, and the investigation of promising inhibitors that can potentially be developed for the treatment of human diseases. Transglutaminases, another class of thiol-dependent enzymes, are not discussed here.
Keywords: Cysteine proteases, cathepsins, calpain, caspase, rhinovirus-3C and SARS-CoV 3CLpro
Current Medicinal Chemistry
Title: Thiol Proteases: Inhibitors and Potential Therapeutic Targets
Volume: 13 Issue: 5
Author(s): Regis Leung-Toung, Yanqing Zhao, Wanren Li, Tim F. Tam, Khashayar Karimian and Michael Spino
Affiliation:
Keywords: Cysteine proteases, cathepsins, calpain, caspase, rhinovirus-3C and SARS-CoV 3CLpro
Abstract: A better understanding of the biological roles and the pathological consequences of thiol-dependent enzymes has emerged in recent years, and hence considerable progress has been made in identifying and delineating cysteine proteases that can be considered promising drug targets from those involved in housekeeping functions. Cysteine proteases have been implicated in a wide variety of disease processes ranging from cardiovascular, inflammatory, viral and immunological disorders to cancer. The first milestone in drug development of cysteine protease inhibitors has probably been reached, as IDN-6556 (a broad spectrum caspase inhibitor) has recently received Orphan Drug label by the U.S. Food and Drug Administration for use in the treatment of the patients undergoing liver transplantation and other solid organ transplantation. IDN-6556, which blocks apoptosis, is in Phase II human clinical trial in patients undergoing liver transplantation. In addition, more than ten cysteine protease inhibitors are presently at various phases of clinical development/trials for diverse diseases. This review emphasises on the new development from the literature reports since the year 2000 in the exploration of potential cysteine proteases as prospective drug targets, and the investigation of promising inhibitors that can potentially be developed for the treatment of human diseases. Transglutaminases, another class of thiol-dependent enzymes, are not discussed here.
Export Options
About this article
Cite this article as:
Leung-Toung Regis, Zhao Yanqing, Li Wanren, Tam F. Tim, Karimian Khashayar and Spino Michael, Thiol Proteases: Inhibitors and Potential Therapeutic Targets, Current Medicinal Chemistry 2006; 13 (5) . https://dx.doi.org/10.2174/092986706776055733
DOI https://dx.doi.org/10.2174/092986706776055733 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Non-Cardiomyocytes in Heart Regeneration
Current Drug Targets New Vectors and Strategies for Cardiovascular Gene Therapy
Current Gene Therapy Sestrins: A New Kid for Stroke Treatment?
Current Drug Delivery Facing Up the ROS Labyrinth - Where To Go?
Current Vascular Pharmacology MMP Inhibitors in Cardiac Diseases: An Update
Recent Patents on Cardiovascular Drug Discovery IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression
Current Drug Targets The Role of Chemokines, Cytokines and Adhesion Molecules in Stem Cell Trafficking and Homing
Current Pharmaceutical Design The Toll-Like Receptor Radical Cycle Pathway: A New Drug Target in Immune-Related Chronic Fatigue
CNS & Neurological Disorders - Drug Targets Novel Pharmacologic Strategies to Protect the Liver from Ischemia- Reperfusion Injury
Recent Patents on Cardiovascular Drug Discovery Novel Therapeutic Approaches in Limiting Oxidative Stress and Inflammation
Current Pharmaceutical Biotechnology An Insight Into Mitochondrial Dysfunction and its Implications in Neurological Diseases
Current Drug Targets The Role of Toll-Like Receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A New Promising Therapeutic Approach?
CNS & Neurological Disorders - Drug Targets Insulin-Like Growth Factor-1 and its Derivatives: Potential Pharmaceutical Application for Treating Neurological Conditions
Recent Patents on CNS Drug Discovery (Discontinued) Anesthetic Pharmacology for Kidney Transplantation
Current Clinical Pharmacology Is the Modulation of Autophagy the Future in the Treatment of Neurodegenerative Diseases?
Current Topics in Medicinal Chemistry Gut-Brain Axis in Gastric Mucosal Damage and Protection
Current Neuropharmacology A Review on Response of Immune System in Spinal Cord Injury and Therapeutic Agents useful in Treatment
Current Pharmaceutical Biotechnology Chronic Inflammatory Diseases and the Acute Respiratory Distress Syndrome (ARDS)
Current Pharmaceutical Design Protective Effects and Mechanisms of Action of Ulinastatin against Cerebral Ischemia-Reperfusion Injury
Current Pharmaceutical Design Anti-inflammatory Treatment of Acute Coronary Syndromes
Current Pharmaceutical Design