Abstract
The search for proteasome inhibitors began fifteen years ago. These inhibitors proved to be powerful tools for investigating many important cellular processes regulated by the ubiquitin-proteasome pathway. Targeting the proteasome pathway can also lead to new treatments for disorders like cancer, muscular dystrophies, inflammation and immune diseases. This is already true for cancer; the FDA approved bortezomib, a potent proteasome inhibitor, for treating multiple myeloma in 2003, and mantle cell lymphoma in 2006. The chemical structures identified in some of the early proteasome inhibitors have led to the development of new anti-cancer drugs (CEP-18770, Carfilzomib, NPI-0052). All these molecules are covalent bonding inhibitors that react with the catalytic Thr1-Oγ of the three types of active site. This review covers recent developments in medicinal chemistry of natural and synthetic proteasome inhibitors. Advances in non-covalent inhibitors that have no reactive group will be highlighted as they should minimize side-effects. New structures and new modes of action have been recently identified that open the door to new drug candidates for treating a range of diseases.
Keywords: Proteasome, inhibitors, anti-cancer drugs, bortezomib, medicinal chemistry, natural products
Current Topics in Medicinal Chemistry
Title: Proteasome Inhibitors: Recent Advances and New Perspectives In Medicinal Chemistry
Volume: 10 Issue: 3
Author(s): E. Genin, M. Reboud-Ravaux and J. Vidal
Affiliation:
Keywords: Proteasome, inhibitors, anti-cancer drugs, bortezomib, medicinal chemistry, natural products
Abstract: The search for proteasome inhibitors began fifteen years ago. These inhibitors proved to be powerful tools for investigating many important cellular processes regulated by the ubiquitin-proteasome pathway. Targeting the proteasome pathway can also lead to new treatments for disorders like cancer, muscular dystrophies, inflammation and immune diseases. This is already true for cancer; the FDA approved bortezomib, a potent proteasome inhibitor, for treating multiple myeloma in 2003, and mantle cell lymphoma in 2006. The chemical structures identified in some of the early proteasome inhibitors have led to the development of new anti-cancer drugs (CEP-18770, Carfilzomib, NPI-0052). All these molecules are covalent bonding inhibitors that react with the catalytic Thr1-Oγ of the three types of active site. This review covers recent developments in medicinal chemistry of natural and synthetic proteasome inhibitors. Advances in non-covalent inhibitors that have no reactive group will be highlighted as they should minimize side-effects. New structures and new modes of action have been recently identified that open the door to new drug candidates for treating a range of diseases.
Export Options
About this article
Cite this article as:
Genin E., Reboud-Ravaux M. and Vidal J., Proteasome Inhibitors: Recent Advances and New Perspectives In Medicinal Chemistry, Current Topics in Medicinal Chemistry 2010; 10 (3) . https://dx.doi.org/10.2174/156802610790725515
DOI https://dx.doi.org/10.2174/156802610790725515 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Multimodal HDAC Inhibitors with Improved Anticancer Activity
Current Cancer Drug Targets Bronchiolar Disorders In Childhood
Current Pediatric Reviews An Interventional Pulmonologist’s Tool: Endobronchial Ultrasound- Guided Transbronchial Needle Aspiration (EBUS-TBNA) in Thoracic Disease — An Update
Current Respiratory Medicine Reviews Molecular Targets of FTY720 (Fingolimod)
Current Molecular Medicine Tumor-Targeted Drug Delivery with Aptamers
Current Medicinal Chemistry New Molecules and Strategies in the Field of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents A Novel Synthesis Method of Apogossypolone and its Antitumor Activity
Letters in Drug Design & Discovery Role of Rap2 and its Downstream Effectors in Tumorigenesis
Anti-Cancer Agents in Medicinal Chemistry The Delivery of Biologically Active (Therapeutic) Peptides and Proteins into Cells
Current Medicinal Chemistry Preface
Current Pharmaceutical Biotechnology Mutations of Chromatin Structure Regulating Genes in Human Malignancies
Current Protein & Peptide Science miRNA: Small Molecules as Potential Novel Biomarkers in Cancer
Current Medicinal Chemistry Differentiation of Glioblastoma and Lymphoma Using Feature Extraction and Support Vector Machine
CNS & Neurological Disorders - Drug Targets Diet and Heart Health: Moderate Wine Drinking Strengthens the Cardioprotective Effects of Fish Consumption
Current Pharmaceutical Biotechnology Designed Multiple Ligands: Basic Research vs Clinical Outcomes
Current Medicinal Chemistry Halogen Atoms in the Modern Medicinal Chemistry: Hints for the Drug Design
Current Drug Targets Role of Chemokines and Their Receptors in Cancer
Current Pharmaceutical Design Signal Transduction Inhibitors as Radiosensitizers
Current Medicinal Chemistry - Anti-Cancer Agents γ δ T Cell Modulation in Anticancer Treatment
Current Cancer Drug Targets G Protein-Coupled Receptor Fusion Proteins in Drug Discovery
Current Pharmaceutical Design