Abstract
Thirteen papain-like cysteine proteases (cathepsins) are coded in the human genome from which two represent pseudogenes. Initially it was believed that lysosomal cysteine proteases primarily fulfill house-keeping functions which would exclude them as potential drug targets. Within the last decade, this view has dramatically changed and highly specific and therapeutically relevant functions have been assigned to individual cathepsins. Cathepsins are critical for osteoclast-mediated bone resorption and cartilage erosion in arthritis. They are involved in various aspects of immune responses, in the development and proliferation of various cell types, as well as in tumor invasion and metastasis. Cathepsins qualify as pharmaceutical targets for the treatment of osteoporosis, arthritis, asthma, autoimmune diseases, and potentially for certain forms of cancer. The major challenge in using cysteine protease inhibitors will be the design of highly selective, potent, and bioavailable compounds. Emerging novel functions of long-known and recently discovered cathepsins will require more emphasis on the selectivity of drug candidates to avoid adverse side effects. This review will focus on the discussion of presently known functions of papain-like cathepsins and on recent advances in the design of cysteine protease inhibitors.
Keywords: lactam, cathepsin, cysteine protease, cathepsin k, protease inhibitor
Current Pharmaceutical Design
Title: Thiol-Dependent Cathepsins: Pathophysiological Implications and Recent Advances in Inhibitor Design
Volume: 8 Issue: 18
Author(s): Dieter Bromme and Jadwiga Kaleta
Affiliation:
Keywords: lactam, cathepsin, cysteine protease, cathepsin k, protease inhibitor
Abstract: Thirteen papain-like cysteine proteases (cathepsins) are coded in the human genome from which two represent pseudogenes. Initially it was believed that lysosomal cysteine proteases primarily fulfill house-keeping functions which would exclude them as potential drug targets. Within the last decade, this view has dramatically changed and highly specific and therapeutically relevant functions have been assigned to individual cathepsins. Cathepsins are critical for osteoclast-mediated bone resorption and cartilage erosion in arthritis. They are involved in various aspects of immune responses, in the development and proliferation of various cell types, as well as in tumor invasion and metastasis. Cathepsins qualify as pharmaceutical targets for the treatment of osteoporosis, arthritis, asthma, autoimmune diseases, and potentially for certain forms of cancer. The major challenge in using cysteine protease inhibitors will be the design of highly selective, potent, and bioavailable compounds. Emerging novel functions of long-known and recently discovered cathepsins will require more emphasis on the selectivity of drug candidates to avoid adverse side effects. This review will focus on the discussion of presently known functions of papain-like cathepsins and on recent advances in the design of cysteine protease inhibitors.
Export Options
About this article
Cite this article as:
Bromme Dieter and Kaleta Jadwiga, Thiol-Dependent Cathepsins: Pathophysiological Implications and Recent Advances in Inhibitor Design, Current Pharmaceutical Design 2002; 8 (18) . https://dx.doi.org/10.2174/1381612023394179
DOI https://dx.doi.org/10.2174/1381612023394179 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Pharmacogenomics of Cytochrome P450 Enzymes in Tumours
Current Pharmacogenomics Disease-Responsive Drug Delivery: The Next Generation of Smart Delivery Devices
Current Drug Metabolism Oesophagogastric Disconnection: Who, How and When? A Review Article
Current Pediatric Reviews Synthetic and Mechanistic Study on the Microwave Assisted Fries Rearrangement of 1-Methylidene-3,4-dihydroisoquinoline-2(1H)-yl-methanones
Current Organic Chemistry Hemolysis-Associated Pulmonary Hypertension in Sickle Cell Disease: Global Disruption of the Arginine-Nitric Oxide Pathway
Current Hypertension Reviews Phage Display Derived Therapeutic Antibodies
Current Pharmaceutical Biotechnology Episcleritis and Scleritis in Rheumatic Disease
Current Rheumatology Reviews Overview of Medicinally Important Diterpenoids Derived from Plastids
Mini-Reviews in Medicinal Chemistry New Insight Into A1 Adenosine Receptors in Diabetes Treatment
Current Pharmaceutical Design Chymase Inhibitors
Current Pharmaceutical Design Natural Products as Anti-glycation Agents: Possible Therapeutic Potential for Diabetic Complications
Current Diabetes Reviews The Prevalence of Frailty in Patients Admitted to Hospital with Vertebral Fragility Fractures
Current Rheumatology Reviews The Potential of Ellagic Acid as a Possible Antimalarial Drug Candidate
Current Bioactive Compounds Role of Beta2 Agonists in Respiratory Medicine with Particular Attention to Novel Patents and Effects on Endocrine System and Immune Response
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Inhaled Corticosteroids and Pneumonia in Chronic Obstructive Pulmonary Disease
Current Respiratory Medicine Reviews Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Development and Optimization of Press Coated Floating Pulsatile Drug Delivery of Sumatriptan Succinate
Current Drug Delivery Recent Advances in the Mechanisms of Action and Physiological Functions of the Retinoid-Related Orphan Receptors (RORs)
Current Drug Targets - Inflammation & Allergy Edtorial [Hot topic: Glucocorticoids from Chemistry to Clinics (Executive Editor: Fortunato Vesce)]
Current Pharmaceutical Design Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders - A Review
Recent Patents on Inflammation & Allergy Drug Discovery