Abstract
TNF-α neutralising agents such as Infliximab (Remicade®), Etanercept (Enbrel®) and the IL-1 receptor antagonist Anakinra (Kineret®), are currently used clinically for the treatment of many inflammatory diseases such as Crohns disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, need to be injected and can cause allergic reactions. An alternative approach to lowering the levels of TNF-α and IL- 1β in inflammatory disease, is to inhibit the enzymes that generate these cytokines using cheaper small molecules. This paper is a broad overview of the progress that has been achieved so far, with respect to small molecule inhibitor design and pharmacological studies (in animals and humans), for the metalloprotease Tumour Necrosis Factor-α Converting Enzyme (TACE) and the cysteine protease Caspase-1 (Interleukin-1β Converting Enzyme, ICE). Inhibitors of these two enzymes are currently considered to be good therapeutic targets that have the potential to provide relatively inexpensive and orally bioavailable anti-inflammatory agents in the future.
Current Medicinal Chemistry
Title: Inhibitors of TACE and Caspase-1 As Anti-inflammatory Drugs
Volume: 12 Issue: 25
Author(s): Giang T. Le and Giovanni Abbenante
Affiliation:
Keywords: protease, tace, caspase-1, ice, inhibitor, review
Abstract: TNF-α neutralising agents such as Infliximab (Remicade®), Etanercept (Enbrel®) and the IL-1 receptor antagonist Anakinra (Kineret®), are currently used clinically for the treatment of many inflammatory diseases such as Crohns disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, need to be injected and can cause allergic reactions. An alternative approach to lowering the levels of TNF-α and IL- 1β in inflammatory disease, is to inhibit the enzymes that generate these cytokines using cheaper small molecules. This paper is a broad overview of the progress that has been achieved so far, with respect to small molecule inhibitor design and pharmacological studies (in animals and humans), for the metalloprotease Tumour Necrosis Factor-α Converting Enzyme (TACE) and the cysteine protease Caspase-1 (Interleukin-1β Converting Enzyme, ICE). Inhibitors of these two enzymes are currently considered to be good therapeutic targets that have the potential to provide relatively inexpensive and orally bioavailable anti-inflammatory agents in the future.
Export Options
About this article
Cite this article as:
Le T. Giang and Abbenante Giovanni, Inhibitors of TACE and Caspase-1 As Anti-inflammatory Drugs, Current Medicinal Chemistry 2005; 12 (25) . https://dx.doi.org/10.2174/092986705774462851
DOI https://dx.doi.org/10.2174/092986705774462851 |
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
-
Aluminum Excytotoxicity and NeuroAutotoImmunity: The Role of the Brain Expression of CD32+ (FcγRIIa), ICAM-1+ and CD3ع in Aging
Current Aging Science Progress in the Oral Treatment of Type 2 Diabetes: Update on DPP-IV Inhibitors
Current Diabetes Reviews Thymoquinone Shows the Diverse Therapeutic Actions by Modulating Multiple Cell Signaling Pathways: Single Drug for Multiple Targets
Current Pharmaceutical Biotechnology The Therapeutic Potential of PhospholipaseA2 Inhibitors in Cardiovascular Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry New Insights into Adipokines as Potential Biomarkers for Type-2 Diabetes Mellitus
Current Medicinal Chemistry Radziszewski Reaction: An Elegant, Easy, Simple and Efficient Method to Synthesise Imidazoles
Current Organic Synthesis In Vitro Models for the Study of Non-Alcoholic Fatty Liver Disease
Current Medicinal Chemistry Imaging of Cyclooxygenase-2 (COX-2) Expression: Potential Use in Diagnosis and Drug Evaluation
Current Pharmaceutical Design Synergistic Effect of Curcumin: A Review
Current Bioactive Compounds Virally Encoded G Protein-Coupled Receptors: Targets for Potentially Innovative Anti-Viral Drug Development
Current Drug Targets Gastroduodenal Safety of Cyclooxygenase-2 Inhibitors
Current Pharmaceutical Design Adipokines and Adipocyte Targets in the Future Management of Obesity and the Metabolic Syndrome
Mini-Reviews in Medicinal Chemistry The Genetic Basis of Graves Disease
Current Genomics Targeting IAPs as An Approach to Anti-Cancer Therapy
Current Topics in Medicinal Chemistry Preclinical Profile of Bacopasides From Bacopa monnieri (BM) As An Emerging Class of Therapeutics for Management of Chronic Pains
Current Medicinal Chemistry Targeting B Cells in SLE: The Experience with Rituximab Treatment (Anti-CD20)
Endocrine, Metabolic & Immune Disorders - Drug Targets Patent Selections
Recent Patents on Biomarkers Expression, Regulation and Function of Asporin, A Susceptibility Gene in Common Bone and Joint Diseases
Current Medicinal Chemistry Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
Current Topics in Medicinal Chemistry Effects of Physical Exercise on Inflammatory Markers of Atherosclerosis
Current Pharmaceutical Design