Abstract
Tumor vasculature is an important target in cancer treatment. Two distinct vasculartargeting therapeutic strategies are applied to attack cancer cells indirectly. The antiangiogenic approach intervenes in the neovascularization processes and blocks the formation of new blood vessels, while th e antivascular approach targets the established tumor blood vessels, making vascular shutdown and resulting in rapid haemorrhagic necrosis and tumor cell death. A number of compounds with diverse structural scaffolds have been designed to target tumor vasculature and they are called vascular disrupting agents (VDAs). The biological or ligand-directed VDAs utilize antibodies, peptides or growth factors to deliver toxins or pro-coagulants or proapoptotic affectors to tumor-related blood vessels, while the small-molecule VDAs selectively target tumor blood vessels and have little effects on the normal endothelium. Among the small-molecule VDAs, the tubulin colchicine binding site inhibitors have been extensively studied and many of them have entered the clinical trials, including CA-4P, CA-1P, AVE8062, OXi4503, CKD-516, BNC105P, ABT-751, CYT- 997, ZD6126, NPI-2358, MN-029 and EPC2407. This review makes a summary of the small-molecule VDAs in clinical developments and highlights some potential VDA leads or candidates for the treatment of tumors.
Keywords: Anticancer, antitumor, antivascular, clinical trials, colchicine binding site, tubulin inhibitors, vascular disrupting agents (VDAs).
Current Medicinal Chemistry
Title:Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments
Volume: 22 Issue: 11
Author(s): Ya-Ting Ji, Yan-Na Liu and Zhao-Peng Liu
Affiliation:
Keywords: Anticancer, antitumor, antivascular, clinical trials, colchicine binding site, tubulin inhibitors, vascular disrupting agents (VDAs).
Abstract: Tumor vasculature is an important target in cancer treatment. Two distinct vasculartargeting therapeutic strategies are applied to attack cancer cells indirectly. The antiangiogenic approach intervenes in the neovascularization processes and blocks the formation of new blood vessels, while th e antivascular approach targets the established tumor blood vessels, making vascular shutdown and resulting in rapid haemorrhagic necrosis and tumor cell death. A number of compounds with diverse structural scaffolds have been designed to target tumor vasculature and they are called vascular disrupting agents (VDAs). The biological or ligand-directed VDAs utilize antibodies, peptides or growth factors to deliver toxins or pro-coagulants or proapoptotic affectors to tumor-related blood vessels, while the small-molecule VDAs selectively target tumor blood vessels and have little effects on the normal endothelium. Among the small-molecule VDAs, the tubulin colchicine binding site inhibitors have been extensively studied and many of them have entered the clinical trials, including CA-4P, CA-1P, AVE8062, OXi4503, CKD-516, BNC105P, ABT-751, CYT- 997, ZD6126, NPI-2358, MN-029 and EPC2407. This review makes a summary of the small-molecule VDAs in clinical developments and highlights some potential VDA leads or candidates for the treatment of tumors.
Export Options
About this article
Cite this article as:
Ji Ya-Ting, Liu Yan-Na and Liu Zhao-Peng, Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments, Current Medicinal Chemistry 2015; 22 (11) . https://dx.doi.org/10.2174/0929867322666150114163732
DOI https://dx.doi.org/10.2174/0929867322666150114163732 |
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
-
Raxofelast, (±)5-(Acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic Acid: A New Antioxidant to Modulate the Inflammatory Response During Ischemia-Reperfusion Injury and Impaired Wound Healing
Mini-Reviews in Medicinal Chemistry A Novel Assay Platform for the Detection of Translation Modulators of Spermidine/ Spermine Acetyltransferase
Current Pharmaceutical Design Nephroangiosclerosis and Its Pharmacological Approach
Current Vascular Pharmacology Nuclear Imaging of Post-infarction Inflammation in Ischemic Cardiac Diseases - New Radiotracers for Potential Clinical Applications
Current Radiopharmaceuticals An Insight of Novel Pharmacological Therapies in Hypertrophic Cardiomyopathy
Medicinal Chemistry Platelet Activation in Atherogenesis Associated with Low-Grade Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Aspartate and Glutamate Mimetic Structures in Biologically Active Compounds
Current Medicinal Chemistry Chondroitin Sulfate Glycosaminoglycans for CNS Homeostasis-Implications for Material Design
Current Medicinal Chemistry Dexmedetomidine: A Review of its Use for the Management of Pain, Agitation, and Delirium in the Intensive Care Unit
Current Pharmaceutical Design The Importance of Gender Differences in the Diagnosis and Management of Cardiovascular Disease
Current Pharmaceutical Design Editorial: New Therapetic Approaches in the Management of Ischemia Reperfusion Injury and Cardiometabolic Diseases: Opportunities and Challenges
Current Drug Targets The mir-221/222 Cluster is a Key Player in Vascular Biology via the Fine-Tuning of Endothelial Cell Physiology
Current Vascular Pharmacology Cardiovascular Complications of HIV Infection and Treatment
Cardiovascular & Hematological Agents in Medicinal Chemistry Gene Therapy Targeting Inflammation in Atherosclerosis
Current Pharmaceutical Design New Inotropic Pharmacologic Strategies Targeting the Failing Myocardiumin the Newborn and Infant
Mini-Reviews in Medicinal Chemistry Translational Application of Combining Magnetic Resonance Imaging and Biomechanical Analysis in Carotid Plaque Vulnerability Assessment
Recent Patents on Medical Imaging Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease
Current Neurovascular Research Extracellular Vesicles as Drug Delivery Vehicles for Rheumatoid Arthritis
Current Stem Cell Research & Therapy Hyperglycemia and Perioperative Glucose Management
Current Pharmaceutical Design Gene Delivery for Periodontal Tissue Engineering: Current Knowledge – Future Possibilities
Current Gene Therapy