Abstract
Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix. MMPs are capable of degrading essentially all matrix components, which is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. The vertebrates MMP family includes at least 26 enzymes (23 have been known in humans) with only MMP-1, 2, and 7 experimentally validated as targets for antitumoral drug design. However, inhibition of MMP-1 has been hypothesized to be the cause of the clinically observed musculoskeletal syndrome when broad spectrum inhibitors are used. On the other hand, MMP-9 is a tricky enzyme, since its inhibition might be useful in treating patients with early-stage cancers, but MMP-9 is an anti-target in patients with advanced disease. So, MMP-9 inhibition should also be prevented. Therefore, selective MMP-2 inhibition arises as a pursued profile for MMP binders. Among them, hydroxamates have been extensively studied as small molecule drug candidates characterized by an effective zinc-binding group plus additional side chains responsible for the selectivity. This article pays particular attention to MMP-2 selectivity on hydroxamate-type inhibitors, especially against MMP-9, and their chemical structure, SAR, general synthetic methods, and molecular modelling studies are here reviewed in order to inspire further design of new effective anticancer agents.
Keywords: Hydroxamate, selective matrix metalloproteinase-2 inhibitors, synthesis, molecular modelling, matrix metalloproteinases, endopeptidases, malignant tumor growth, invasion, metastasis, angiogenesis
Current Medicinal Chemistry
Title: MMP-2 Selectivity in Hydroxamate-Type Inhibitors
Volume: 19 Issue: 7
Author(s): P. Serra, M. Bruczko, J. M. Zapico, A. Puckowska, M. A. Garcia, S. Martin-Santamaria, A. Ramos and B. de Pascual-Teresa
Affiliation:
Keywords: Hydroxamate, selective matrix metalloproteinase-2 inhibitors, synthesis, molecular modelling, matrix metalloproteinases, endopeptidases, malignant tumor growth, invasion, metastasis, angiogenesis
Abstract: Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix. MMPs are capable of degrading essentially all matrix components, which is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. The vertebrates MMP family includes at least 26 enzymes (23 have been known in humans) with only MMP-1, 2, and 7 experimentally validated as targets for antitumoral drug design. However, inhibition of MMP-1 has been hypothesized to be the cause of the clinically observed musculoskeletal syndrome when broad spectrum inhibitors are used. On the other hand, MMP-9 is a tricky enzyme, since its inhibition might be useful in treating patients with early-stage cancers, but MMP-9 is an anti-target in patients with advanced disease. So, MMP-9 inhibition should also be prevented. Therefore, selective MMP-2 inhibition arises as a pursued profile for MMP binders. Among them, hydroxamates have been extensively studied as small molecule drug candidates characterized by an effective zinc-binding group plus additional side chains responsible for the selectivity. This article pays particular attention to MMP-2 selectivity on hydroxamate-type inhibitors, especially against MMP-9, and their chemical structure, SAR, general synthetic methods, and molecular modelling studies are here reviewed in order to inspire further design of new effective anticancer agents.
Export Options
About this article
Cite this article as:
Serra P., Bruczko M., M. Zapico J., Puckowska A., A. Garcia M., Martin-Santamaria S., Ramos A. and de Pascual-Teresa B., MMP-2 Selectivity in Hydroxamate-Type Inhibitors, Current Medicinal Chemistry 2012; 19 (7) . https://dx.doi.org/10.2174/092986712799320628
DOI https://dx.doi.org/10.2174/092986712799320628 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
CD44 - a New Cardiovascular Drug Target or Merely an Innocent Bystander?
Cardiovascular & Hematological Disorders-Drug Targets Utilizing Delta Opioid Receptors and Peptides for Cytoprotection: Implications in Stroke and Other Neurological Disorders
CNS & Neurological Disorders - Drug Targets Novel Imaging Techniques in Acute Kidney Injury
Current Drug Targets Editorial: microRNAs: Potential Targets for the Treatment of Cardiovascular Disease
Current Vascular Pharmacology The Wnt/β-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity
Current Neurovascular Research Implications of microRNAs in the Pathogenesis of Atherosclerosis and Prospects for Therapy
Current Drug Targets Adenosine Myocardial Perfusion Imaging
Current Medical Imaging miR-666-3p Mediates the Protective Effects of Mesenchymal Stem Cell-derived Exosomes Against Oxygen-glucose Deprivation and Reoxygenation- induced Cell Injury in Brain Microvascular Endothelial Cells via Mitogen-activated Protein Kinase Pathway
Current Neurovascular Research miR-29c-3p is an Effective Biomarker of Abdominal Aortic Aneurysm in Patients Undergoing Elective Surgery
MicroRNA Graphical Abstracts:
Current Medical Imaging Does Pharmacological Therapy Still Play a Role in Preventing Sudden Death in Surgically Treated Tetralogy of Fallot?
Mini-Reviews in Medicinal Chemistry Alanine Aminotransferase Predicts Outcomes in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage
Current Neurovascular Research Targeting PPAR Isoforms Following CNS Injury
Current Drug Targets Neurocysticercosis: The Enigmatic Disease
Central Nervous System Agents in Medicinal Chemistry Exploring the use of Estrogen & Progesterone Replacement Therapy in Subarachnoid Hemorrhage
Current Drug Safety Extraction of Quantitative Anatomical Information from Coronary Angiographies
Current Bioinformatics Extracellular Matrix on the Phenotypic Switching of Vascular Smooth Muscle Cells
Current Angiogenesis (Discontinued) Inflammatory Events Following Subarachnoid Hemorrhage (SAH)
Current Neuropharmacology The High Potency of Polymeric Nanoparticles in the Drug Delivery System for Hypertension Treatment: A Systematic Review
Current Hypertension Reviews The Immune System and the Brain: Crosstalk with a Broad Impact From Host Defense to Cognition
Current Neurovascular Research