Abstract
Biological thiol-dependent enzymes have recently received extensive attention in the literature because of their involvement in a variety of physiopathological conditions. The active thiol groups of these enzymes are derived from the cysteine residues present. Hence, in a biological system, the selective reversible or irreversible inhibition of the activity of these enzymes by modification of the thiol moiety may potentially lead to the development of a chemotherapeutic treatment. Despite all the research efforts involved in the attempt to develop potential chemotherapeutic treatments for the major diseases involving cysteine proteases, there are in fact no such treatments available yet. However, AG7088 (1) an inhibitor of rhinovirus-3C is in phase II / III clinical trial for the treatment of common cold and VX-740 (2, pralnacasan) an inhibitor of caspase-1 is in phase II clinical trial as an anti-inflammatory agent for rheumatoid arthritis. Several other cysteine protease inhibitors (i.e., cathepsin K, and S) are in pre-clinical evaluation or preclinical development. Structure-based drug design approaches have been instrumental in the development of these inhibitors. Intensive biochemical studies on the cysteine proteases have shed some light on some potential targets for therapeutic development. In addition, new techniques and new ideas are constantly emerging. As such, an up-to-date review of the literature on thiol-dependent enzymes as potential targets and their inhibitors designed from peptidic, modified peptidomimetic scaffolds and from small heterocyclic molecules is presented.
Keywords: thiol-dependent enzymes, cysteine proteases, cathepsins, falcipain, cruzain, calpain, caspase, rhinovirus-3c, inhibitors
Current Medicinal Chemistry
Title: Thiol-Dependent Enzymes and Their Inhibitors: A Review
Volume: 9 Issue: 9
Author(s): Regis Leung-Toung, Wanren Li, Tim F. Tam and Khashayar Kaarimian
Affiliation:
Keywords: thiol-dependent enzymes, cysteine proteases, cathepsins, falcipain, cruzain, calpain, caspase, rhinovirus-3c, inhibitors
Abstract: Biological thiol-dependent enzymes have recently received extensive attention in the literature because of their involvement in a variety of physiopathological conditions. The active thiol groups of these enzymes are derived from the cysteine residues present. Hence, in a biological system, the selective reversible or irreversible inhibition of the activity of these enzymes by modification of the thiol moiety may potentially lead to the development of a chemotherapeutic treatment. Despite all the research efforts involved in the attempt to develop potential chemotherapeutic treatments for the major diseases involving cysteine proteases, there are in fact no such treatments available yet. However, AG7088 (1) an inhibitor of rhinovirus-3C is in phase II / III clinical trial for the treatment of common cold and VX-740 (2, pralnacasan) an inhibitor of caspase-1 is in phase II clinical trial as an anti-inflammatory agent for rheumatoid arthritis. Several other cysteine protease inhibitors (i.e., cathepsin K, and S) are in pre-clinical evaluation or preclinical development. Structure-based drug design approaches have been instrumental in the development of these inhibitors. Intensive biochemical studies on the cysteine proteases have shed some light on some potential targets for therapeutic development. In addition, new techniques and new ideas are constantly emerging. As such, an up-to-date review of the literature on thiol-dependent enzymes as potential targets and their inhibitors designed from peptidic, modified peptidomimetic scaffolds and from small heterocyclic molecules is presented.
Export Options
About this article
Cite this article as:
Leung-Toung Regis, Li Wanren, Tam F. Tim and Kaarimian Khashayar, Thiol-Dependent Enzymes and Their Inhibitors: A Review, Current Medicinal Chemistry 2002; 9 (9) . https://dx.doi.org/10.2174/0929867024606704
DOI https://dx.doi.org/10.2174/0929867024606704 |
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
- 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
-
P2X7 Receptor-Associated Programmed Cell Death in the Pathophysiology of Hemorrhagic Stroke
Current Neuropharmacology Plasma Potassium Levels in Healthy Prehypertension Subjects and the Role of A High Potassium Drink
Current Hypertension Reviews Mechanisms of Corticosteroid Resistance in Severe Asthma and Chronic Obstructive Pulmonary Disease (COPD)
Current Pharmaceutical Design Involvement of Leukotriene Pathway in the Pathogenesis of Ischemia- Reperfusion Injury and Septic and Non-Septic Shock
Current Vascular Pharmacology New Aspects of Regulatory Signaling Pathways and Novel Therapies in Pancreatic Cancer
Current Molecular Medicine Alpha-1 Antitrypsin Deficiency: Current Perspective from Genetics to Diagnosis and Therapeutic Approaches
Current Medicinal Chemistry Thymoquinone Shows the Diverse Therapeutic Actions by Modulating Multiple Cell Signaling Pathways: Single Drug for Multiple Targets
Current Pharmaceutical Biotechnology Design, Synthesis, and Docking Studies of 4H-Chromene and Chromene Based Azo Chromophores: A Novel Series of Potent Antimicrobial and Anticancer Agents
Current Organic Synthesis Selective Neuronal Nitric Oxide Synthase Inhibitors
Current Topics in Medicinal Chemistry Chondroitin Sulfate and Sulfur Containing Chondroprotective Agents: Is there a Basis for their Pharmacological Action?
Current Rheumatology Reviews NF-κB as a Therapeutic Target for Transcription Factor Decoy Strategy in Inflammatory Diseases
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Effect of Simvastatin on Inflammatory Cytokines Balance in Air Pouch Granuloma Model
Inflammation & Allergy - Drug Targets (Discontinued) Prerequisite of a Holistic Blend of Traditional and Modern Approaches of Cancer Management
Current Cancer Therapy Reviews The Role of Endocannabinoids in Pain Modulation and the Therapeutic Potential of Inhibiting their Enzymatic Degradation
Current Pharmaceutical Biotechnology Current Pharmacological Approach to Restore Endothelial Dysfunction
Cardiovascular & Hematological Agents in Medicinal Chemistry Therapeutic Targets for Management of Periodontitis and Diabetes
Current Pharmaceutical Design Interrelationships Among Gut Microbiota and Host: Paradigms, Role in Neurodegenerative Diseases and Future Prospects
CNS & Neurological Disorders - Drug Targets Atherosclerosis is an Inflammatory Disorder After All
Current Topics in Medicinal Chemistry Carbohydrate Antigens: Synthesis Aspects and Immunological Applications in Cancer
Mini-Reviews in Medicinal Chemistry Free Radicals Generated by Post-Prandial Oxidative Burst in the Early Alterations of Vascular Contractility
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued)