Abstract
Matrix metalloproteinases (MMPs) belong to a family of closely related calcium- and zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix (ECM) proteins that are associated with the tumorigenic processes. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function. Thus, MMP inhibitors (MMPIs) are expected to be useful chemotherapeutic agents for the treatment of malignant cancer, osteoarthritis, and rheumatoid arthritis. A vast number of small molecular MMPIs have been developed in recent years. Although there have been considerable preclinical and clinical studies on these inhibitors, most of the effective candidates in clinical trials, however, have yielded unsatisfactory results, thus they are as yet unavailable for use as therapeutic drugs. Currently, more efforts have been directed to the design of specific inhibitors towards certain MMP family members for selective usage. This review will focus primarily on an analysis of recent developed MMPIs that have entered preclinical or clinical trials, and recently registered patents with regard to new highly selective MMPIs in USA or patent applications related to the specific inhibitors of MMPs. We also analyze the clinical failure and discuss the possible strategies to best optimize the development of these novel agents.
Keywords: Matrix metalloproteinases (MMPs), inhibitors, specific, selectivity
Recent Patents on Anti-Cancer Drug Discovery
Title: Recent Developments in Patent Anti-Cancer Agents Targeting the Matrix Metalloproteinases (MMPs)
Volume: 5 Issue: 2
Author(s): Xun Li and Ji-Feng Wu
Affiliation:
Keywords: Matrix metalloproteinases (MMPs), inhibitors, specific, selectivity
Abstract: Matrix metalloproteinases (MMPs) belong to a family of closely related calcium- and zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix (ECM) proteins that are associated with the tumorigenic processes. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function. Thus, MMP inhibitors (MMPIs) are expected to be useful chemotherapeutic agents for the treatment of malignant cancer, osteoarthritis, and rheumatoid arthritis. A vast number of small molecular MMPIs have been developed in recent years. Although there have been considerable preclinical and clinical studies on these inhibitors, most of the effective candidates in clinical trials, however, have yielded unsatisfactory results, thus they are as yet unavailable for use as therapeutic drugs. Currently, more efforts have been directed to the design of specific inhibitors towards certain MMP family members for selective usage. This review will focus primarily on an analysis of recent developed MMPIs that have entered preclinical or clinical trials, and recently registered patents with regard to new highly selective MMPIs in USA or patent applications related to the specific inhibitors of MMPs. We also analyze the clinical failure and discuss the possible strategies to best optimize the development of these novel agents.
Export Options
About this article
Cite this article as:
Li Xun and Wu Ji-Feng, Recent Developments in Patent Anti-Cancer Agents Targeting the Matrix Metalloproteinases (MMPs), Recent Patents on Anti-Cancer Drug Discovery 2010; 5 (2) . https://dx.doi.org/10.2174/157489210790936234
DOI https://dx.doi.org/10.2174/157489210790936234 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
Call for Papers in Thematic Issues
Novel anti-cancer drugs in photoimmunotherapy management: from bench to translational research
In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...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
Related Articles
-
PEGylation of Proteins and Liposomes: a Powerful and Flexible Strategy to Improve the Drug Delivery
Current Drug Metabolism Progress in Studies of Structure, Mechanism and Antagonists Interaction of GPCR Co-Receptors for HIV
Current Pharmaceutical Biotechnology The Multi-faceted Profile of Corticotropin-releasing Factor (CRF) Family of Neuropeptides and of their Receptors on the Paracrine/Local Regulation of the Inflammatory Response
Current Molecular Pharmacology Choosing between Targeted Therapies for Rheumatoid Arthritis Patients: The Oncology Perspective
Current Rheumatology Reviews Oxidative Stress in the Pathogenesis/Treatment of Diabetes and its Complications
Current Nutrition & Food Science NFAT Gene Family in Inflammation and Cancer
Current Molecular Medicine The Potential use of Dendritic Cell-based Immunotherapy for Treatment of Pancreatic Cancer
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Pivotal Roles of Interleukin-17 as the Epicenter of Bone Loss Diseases
Current Pharmaceutical Design Evaluation of in vivo Anti-inflammatory and Analgesic Activities of Novel Derivatives of Ugi-4CR
Mini-Reviews in Medicinal Chemistry Pain Alleviation in Anti-Inflammatory and Anti-Allergic Conditions
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Impact of Worms and their Products on Eosinophils and Neutrophils in Experimental Asthma
Current Molecular Medicine Common Molecular Targets for Bioactive Food Components and Drugs
Current Pediatric Reviews Chemical and Pharmacological Significance of Natural Guanidines from Marine Invertebrates
Mini-Reviews in Medicinal Chemistry Peripheral Anti-nociceptive and Anti-inflammatory Effect of Oleanolic Acid in a Rat Model of Osteoarthritis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry New Insights for Multifactorial Disease Therapy: The Challenge of the Symbiotic Drugs
Current Drug Therapy Progress Towards the Identification of New Aggrecanase Inhibitors
Current Medicinal Chemistry Fibromyalgia: Mechanisms, Current Treatment and Animal Models
Current Pharmaceutical Biotechnology Anti-Inflammatory Agents in Ageing and Age-Associated Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Defensive and Offensive Cross-Reactive Antibodies Elicited by Pathogens: The Good, the Bad and the Ugly
Current Medicinal Chemistry Every Cloud Has a Silver Lining: Proneurogenic Effects of Aβ Oligomers and HMGB-1 via Activation of the RAGE-NF-κB Axis
CNS & Neurological Disorders - Drug Targets