Abstract
Calpain is unique among the cysteine protease family of enzymes in that it combines thiol protease activity with calmodulin-like activity. Despite its wide spread distribution the exact physiological function(s) of calpain is yet to be deciphered. The enzyme is however, implicated in a number of pathophysiological conditions. Due to the potential of calpain as a therapeutic target a number of inhibitors have been described for the enzyme. In this article we have grouped calpain inhibitors into those derived from natural sources, and those derived from chemical synthesis. Additionally, an overview of functional groups that have been used as “warheadso of calpain inhibitors is presented along with a discussion of the structure activity relationship studies of the address region of peptidyl calpain inhibitors. Recent work in this area has led to a better understanding of the structural requirements for tight binding of inhibitors to the active site of calpain. A discussion of peptidomimetic calpain inhibitors, nonpeptide calpain inhibitors, and selectivity of some calpain inhibitors are also presented. The recent disclosure of the crystal structure of a nonpeptide calpain inhibitor bound to a hydrophobic pocket on the calcium-binding domain of calpain has opened the door to future development of potent cell permeable nonpeptide calpain inhibitors.
Current Medicinal Chemistry
Title: A Survey of Calpain Inhibitors
Volume: 7 Issue: 12
Author(s): I. O. Donkor
Affiliation:
Abstract: Calpain is unique among the cysteine protease family of enzymes in that it combines thiol protease activity with calmodulin-like activity. Despite its wide spread distribution the exact physiological function(s) of calpain is yet to be deciphered. The enzyme is however, implicated in a number of pathophysiological conditions. Due to the potential of calpain as a therapeutic target a number of inhibitors have been described for the enzyme. In this article we have grouped calpain inhibitors into those derived from natural sources, and those derived from chemical synthesis. Additionally, an overview of functional groups that have been used as “warheadso of calpain inhibitors is presented along with a discussion of the structure activity relationship studies of the address region of peptidyl calpain inhibitors. Recent work in this area has led to a better understanding of the structural requirements for tight binding of inhibitors to the active site of calpain. A discussion of peptidomimetic calpain inhibitors, nonpeptide calpain inhibitors, and selectivity of some calpain inhibitors are also presented. The recent disclosure of the crystal structure of a nonpeptide calpain inhibitor bound to a hydrophobic pocket on the calcium-binding domain of calpain has opened the door to future development of potent cell permeable nonpeptide calpain inhibitors.
Export Options
About this article
Cite this article as:
Donkor O. I., A Survey of Calpain Inhibitors, Current Medicinal Chemistry 2000; 7 (12) . https://dx.doi.org/10.2174/0929867003374129
DOI https://dx.doi.org/10.2174/0929867003374129 |
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
-
Old Strategies and New Perspectives in Modulating the Endocannabinoid System
Current Bioactive Compounds Can Transcriptomics Cut the Gordian Knot of Amyotrophic Lateral Sclerosis?
Current Genomics Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease
Current Alzheimer Research Neurotrophic Effects of the Peptide NAP: A Novel Neuroprotective Drug Candidate
Current Alzheimer Research Evolving Therapeutic Targets in Ischemic Stroke: A Concise Review
Current Drug Targets Clinical Applications of Mesenchymal Stem Cells in the Treatment of Fracture Non-Union and Bone Defects
Current Stem Cell Research & Therapy Fatty Acids - Induced Lipotoxicity and Inflammation
Current Drug Metabolism New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia
Current Pharmaceutical Design On the Future Development of Optimally-Sized Lipid-Insoluble Systemic Therapies for CNS Solid Tumors and Other Neuropathologies
Recent Patents on CNS Drug Discovery (Discontinued) The Multiple Aspects of Stroke and Stem Cell Therapy
Current Molecular Medicine Histone Deacetylase Inhibitors: New Promise in the Treatment of Immune and Inflammatory Diseases
Current Drug Targets Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology CNS Immune Surveillance and Neuroinflammation: Endocannabinoids Keep Control
Current Pharmaceutical Design Mitochondrial Neuroprotection in Traumatic Brain Injury: Rationale and Therapeutic Strategies
CNS & Neurological Disorders - Drug Targets Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors
Current Neuropharmacology Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure- Activity Relationships of a Neuroprotective Peptide
Current Medicinal Chemistry Oxidation Chemistry of Catecholamines and Neuronal Degeneration: An Update
Current Medicinal Chemistry Update on Cancer Related Issues of Mesenchymal Stem Cell-Based Therapies
Current Stem Cell Research & Therapy Embryonic Stem Cells: A Perfect Marriage Between Gene Regulation and Regenerative Medicine
Current Topics in Medicinal Chemistry Neuropharmacology of Cannabinoid System: From Basic Science to Clinical Applications
Current Neuropharmacology