Abstract
Cathepsin B is an abundant and ubiquitously expressed cysteine peptidase of the papain family. It is involved in many physiological processes, such as remodeling of the extracellular matrix (wound healing), apoptosis, and activation of thyroxine and renin. In addition to its physiological roles, cathepsin B is important in many pathological processes, such as inflammation, parasite infection and cancer, where it is highly up-regulated. In cancer patients, elevated cathepsin B activity correlates to poor therapy outcome. Therefore, it is not surprising that the use of cathepsin B inhibitors reduces both tumor cell motility and invasiveness in vitro. This review summarizes recent developments in cathepsin B inhibition. To date, numerous protein inhibitors of cathepsin B have been described, some of which are of endogenous origin and function as regulators of cathepsin B activity in the cell, such as the cystatins. In addition, some exogenous protein inhibitors of cathepsin B have been isolated from various natural sources, and the use of X-ray crystal structures of cathepsin B complexed with such protein inhibitors has resulted in the design and synthesis of many new small-molecular-weight compounds as inhibitors of cathepsin B. These synthetic compounds generally contain an electrophilic functionality that reacts with cathepsin B. In the present review, these inhibitors are divided according to their mechanisms of action, as reversible and irreversible, and then further subdivided into groups for their full descriptions.
Keywords: cathepsins, cysteine proteases, anticancer drugs, cancer, inhibitors, Cathepsin B
Current Medicinal Chemistry
Title: Inhibitors of Cathepsin B
Volume: 13 Issue: 19
Author(s): S. Gobec and R. Frlan
Affiliation:
Keywords: cathepsins, cysteine proteases, anticancer drugs, cancer, inhibitors, Cathepsin B
Abstract: Cathepsin B is an abundant and ubiquitously expressed cysteine peptidase of the papain family. It is involved in many physiological processes, such as remodeling of the extracellular matrix (wound healing), apoptosis, and activation of thyroxine and renin. In addition to its physiological roles, cathepsin B is important in many pathological processes, such as inflammation, parasite infection and cancer, where it is highly up-regulated. In cancer patients, elevated cathepsin B activity correlates to poor therapy outcome. Therefore, it is not surprising that the use of cathepsin B inhibitors reduces both tumor cell motility and invasiveness in vitro. This review summarizes recent developments in cathepsin B inhibition. To date, numerous protein inhibitors of cathepsin B have been described, some of which are of endogenous origin and function as regulators of cathepsin B activity in the cell, such as the cystatins. In addition, some exogenous protein inhibitors of cathepsin B have been isolated from various natural sources, and the use of X-ray crystal structures of cathepsin B complexed with such protein inhibitors has resulted in the design and synthesis of many new small-molecular-weight compounds as inhibitors of cathepsin B. These synthetic compounds generally contain an electrophilic functionality that reacts with cathepsin B. In the present review, these inhibitors are divided according to their mechanisms of action, as reversible and irreversible, and then further subdivided into groups for their full descriptions.
Export Options
About this article
Cite this article as:
Gobec S. and Frlan R., Inhibitors of Cathepsin B, Current Medicinal Chemistry 2006; 13 (19) . https://dx.doi.org/10.2174/092986706777935122
DOI https://dx.doi.org/10.2174/092986706777935122 |
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
-
miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets Targeting Tumor-Related Immunosuppression for Cancer Immunotherapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Cardiolipin in Mitochondrial Diseases and Apoptosis
Current Medicinal Chemistry Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) ADAM Metalloproteinases as Potential Drug Targets
Current Medicinal Chemistry Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging Signal Transduction and Photodynamic Therapy
Current Signal Transduction Therapy Epigenetic Modulation Using Small Molecules - Targeting Histone Acetyltransferases in Disease
Current Medicinal Chemistry The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Stimulation of Peroxisome Proliferator-Activated Receptor-Gamma (PPARγ) using Pioglitazone Decreases the Survival of Acute Promyelocytic Leukemia Cells through Up-Regulation of PTEN Expression
Anti-Cancer Agents in Medicinal Chemistry Neuropilin Signalling in Vascular Development and Pathology
Current Angiogenesis (Discontinued) Extracorporeal Shock Wave Therapy in Inflammatory Diseases: Molecular Mechanism that Triggers Anti-Inflammatory Action
Current Medicinal Chemistry A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Anti-Cancer Agents in Medicinal Chemistry Brain Segmentation Using Deep Neural Networks
International Journal of Sensors, Wireless Communications and Control Improvement of Nonviral Gene Therapy by Epstein-Barr Virus (EBV)-based Plasmid Vectors
Current Gene Therapy AKT Signaling in Regulating Angiogenesis
Current Cancer Drug Targets TNF-α Inhibitors with Anti-Oxidative Stress Activity from Natural Products
Current Topics in Medicinal Chemistry Ketogenic Diet Acts on Body Remodeling and MicroRNAs Expression Profile
MicroRNA Inhibiting Breast Cancer Progression by Exploiting TGFβ Signaling
Current Drug Targets Immune Responses to Adenovirus and Adeno-Associated Vectors Used for Gene Therapy of Brain Diseases: The Role of Immunological Synapses in Understanding the Cell Biology of Neuroimmune Interactions
Current Gene Therapy