Abstract
Tubulin is one of the most useful and strategic molecular targets for anticancer drugs. The dynamic process of microtubule assembly and disassembly can be blocked by various agents that bind to distinct sites in the β-tubulin subunit. By interfering with microtubule function in vitro, these agents arrest cells in mitosis, eventually leading to cell death, by both apoptosis and necrosis. So far, three binding domains have been identified a) the colchicine site close to the α/β interface, b) the area where the vinca alkaloids bind, and c) the taxane-binding pocket. This review compiles the patent literature up to 2013 and offers a detailed account of all the advances on Tubulin inhibitors (lead molecules) along with in depth knowledge about the number of novel scaffolds, modified analogs and derivatives of the lead molecules. Colchicine binding site remains the most explored site indicated by the patent survey as majority of the patents revolves around phenstatin and combretastatin based molecules where the key structural feature for tubulin inhibition is an appropriate arrangement of the two aromatic rings at an appropriate distance and optimal dihedral angle maximizing interactions with tubulin. A brief account of promising tubulin inhibitors in stages of clinical development and some strategies for the development of potent molecules overcoming the problem of drug resistance have also been discussed.
Keywords: Cancer, chalcones, colchicine, microtubules, tubulin, tumor.
Recent Patents on Anti-Cancer Drug Discovery
Title:Tubulin Inhibitors: A Patent Survey
Volume: 9 Issue: 2
Author(s): Kunal Nepali, Ritu Ojha, Sahil Sharma, Preet M.S. Bedi and Kanaya L. Dhar
Affiliation:
Keywords: Cancer, chalcones, colchicine, microtubules, tubulin, tumor.
Abstract: Tubulin is one of the most useful and strategic molecular targets for anticancer drugs. The dynamic process of microtubule assembly and disassembly can be blocked by various agents that bind to distinct sites in the β-tubulin subunit. By interfering with microtubule function in vitro, these agents arrest cells in mitosis, eventually leading to cell death, by both apoptosis and necrosis. So far, three binding domains have been identified a) the colchicine site close to the α/β interface, b) the area where the vinca alkaloids bind, and c) the taxane-binding pocket. This review compiles the patent literature up to 2013 and offers a detailed account of all the advances on Tubulin inhibitors (lead molecules) along with in depth knowledge about the number of novel scaffolds, modified analogs and derivatives of the lead molecules. Colchicine binding site remains the most explored site indicated by the patent survey as majority of the patents revolves around phenstatin and combretastatin based molecules where the key structural feature for tubulin inhibition is an appropriate arrangement of the two aromatic rings at an appropriate distance and optimal dihedral angle maximizing interactions with tubulin. A brief account of promising tubulin inhibitors in stages of clinical development and some strategies for the development of potent molecules overcoming the problem of drug resistance have also been discussed.
Export Options
About this article
Cite this article as:
Nepali Kunal, Ojha Ritu, Sharma Sahil, Bedi M.S. Preet and Dhar L. Kanaya, Tubulin Inhibitors: A Patent Survey, Recent Patents on Anti-Cancer Drug Discovery 2014; 9 (2) . https://dx.doi.org/10.2174/15748928113089990042
DOI https://dx.doi.org/10.2174/15748928113089990042 |
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
-
Theranostic Radiopharmaceuticals Targeting Cancer-Associated Fibroblasts
Current Radiopharmaceuticals Transposons for Gene Therapy!
Current Gene Therapy Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology Ceramide and Sphingosine-1-Phosphate in Cell Death Pathways : Relevance to the Pathogenesis of Alzheimer's Disease
Current Alzheimer Research Cheminfomatic-based Drug Discovery of Human Tyrosine Kinase Inhibitors
Current Topics in Medicinal Chemistry Breaking the Barrier of Cancer Through Liposome Loaded with Phytochemicals
Current Drug Delivery FOXO1: A Potential Target for Human Diseases
Current Drug Targets Imaging Virus-Associated Cancer
Current Pharmaceutical Design Editorial (Thematic Issue: Role of Antioxidants Treatments on Oxidative Stress and Calcium Entry in Neurological Disease: Focus on TRP Channels)
Current Neuropharmacology Nanoparticle-based Drug Delivery Systems for Solid Brain Tumors
Current Nanoscience Overcoming the Hurdles of Tumor Immunity by Targeting Regulatory Pathways in Innate and Adaptive Immune Cells
Current Pharmaceutical Design Therapeutic Application of Natural Medicine Monomers in Cancer Treatment
Current Medicinal Chemistry Anti-tumor Effects of Curcuminoids in Glioblastoma Multiforme: An Updated Literature Review
Current Medicinal Chemistry TGF-β2 Signaling in High-Grade Gliomas
Current Pharmaceutical Biotechnology New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas
Current Stem Cell Research & Therapy Monoclonal Antibodies Targeting the Epidermal Growth Factor Receptor
Current Drug Targets An Automatic Glioma Segmentation System Using a Multilevel Attention Pyramid Scene Parsing Network
Current Medical Imaging MicroRNA-136 Promotes Vascular Muscle Cell Proliferation Through the ERK1/2 Pathway by Targeting PPP2R2A in Atherosclerosis
Current Vascular Pharmacology Improvement of Tumor Localization of Photosensitizers for Photodynamic Therapy and Its Application for Tumor Diagnosis
Current Topics in Medicinal Chemistry