Abstract
Microtubule drugs have been widely used in cancer chemotherapies. Although microtubules are subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied on compounds that bind to the tubulin subunit. Using a cell-based assay designed to probe the microtubule polymerization status, we identified two pharmacophores, CM09 and CM10, as cell-permeable microtubule stabilizing agents. These synthetic compounds do not affect the assembly state of purified microtubules in vitro but they profoundly suppress microtubule dynamics in vivo. Moreover, they exert cytotoxic effects on several cancer cell lines including multidrug resistant cell lines. Therefore, these classes of compounds represent novel attractive leads for cancer chemotherapy.
Keywords: Chemical biology, high content analysis, microtubule dynamics, microtubule targeting agents, phenotypic screening.
Current Cancer Drug Targets
Title:Novel Synthetic Pharmacophores Inducing a Stabilization of Cellular Microtubules
Volume: 15 Issue: 1
Author(s): Anne Martinez, Emmanuelle Soleilhac, Caroline Barette, Renaud Prudent, Gustavo J. Gozzi, Emilie Vassal-Stermann, Catherine Pillet, Attilio Di Pietro, Marie-Odile Fauvarque and Laurence Lafanechere
Affiliation:
Keywords: Chemical biology, high content analysis, microtubule dynamics, microtubule targeting agents, phenotypic screening.
Abstract: Microtubule drugs have been widely used in cancer chemotherapies. Although microtubules are subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied on compounds that bind to the tubulin subunit. Using a cell-based assay designed to probe the microtubule polymerization status, we identified two pharmacophores, CM09 and CM10, as cell-permeable microtubule stabilizing agents. These synthetic compounds do not affect the assembly state of purified microtubules in vitro but they profoundly suppress microtubule dynamics in vivo. Moreover, they exert cytotoxic effects on several cancer cell lines including multidrug resistant cell lines. Therefore, these classes of compounds represent novel attractive leads for cancer chemotherapy.
Export Options
About this article
Cite this article as:
Martinez Anne, Soleilhac Emmanuelle, Barette Caroline, Prudent Renaud, Gozzi J. Gustavo, Vassal-Stermann Emilie, Pillet Catherine, Pietro Di Attilio, Fauvarque Marie-Odile and Lafanechere Laurence, Novel Synthetic Pharmacophores Inducing a Stabilization of Cellular Microtubules, Current Cancer Drug Targets 2015; 15 (1) . https://dx.doi.org/10.2174/1568009615666141215154149
DOI https://dx.doi.org/10.2174/1568009615666141215154149 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Mining the Genome for Susceptibility to Complex Neurological Disorders
Current Molecular Medicine Modulation of MicroRNAs by <i>Euphorbia Microsciadia</i> Boiss in MDA-MB-231 Cell Line: New Possibilities in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids
Current Medicinal Chemistry Nanotechnology and Animal Health
Pharmaceutical Nanotechnology Therapeutic Effects of Progesterone in Animal Models of Neurological Disorders
CNS & Neurological Disorders - Drug Targets Aromatase Inhibitors: A New Paradigm in Breast Cancer Treatment
Current Medicinal Chemistry - Anti-Cancer Agents New Insights in Testing and Imaging Techniques for Solid Tumor Response Evaluation
Neuroscience and Biomedical Engineering (Discontinued) Drug Targeting to the Brain - A Review
Current Nanoscience Advances in Interleukin-12 Gene Therapy for Acquired Liver Diseases
Current Gene Therapy The Circulating Endothelial Cell in Cancer: Towards Marker and Target Identification
Current Pharmaceutical Design Novel Anti-Cancer Strategy in Bone Tumors by Targeting Molecular and Cellular Modulators of Bone Resorption
Recent Patents on Anti-Cancer Drug Discovery Colorectal Carcinogensis and Suppression of Tumor Development by Inhibition of Enzymes and Molecular Targets
Current Enzyme Inhibition Electrochemotherapy in the Treatment of Kaposi’s Sarcoma: A Single Centre Cohort Study and a Comparison with the Literature Data
Current Cosmetic Science Anticancer Potential of Dietary Natural Products: A Comprehensive Review
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Current Drug Targets Heparin Derivatives as Angiogenesis Inhibitors
Current Pharmaceutical Design Transcriptome and Proteome Analyses of Drug Interactions with Natural Products
Current Drug Metabolism Opposing Functions for the Wilms Tumor Protein 1 (WT1) in Tumorigenesis
Current Pediatric Reviews Wide-Ranging Genomic Effects of Plasticisers and Related Compounds
Current Drug Metabolism The Interactions of Anticancer Agents with Tea Catechins: Current Evidence from Preclinical Studies
Anti-Cancer Agents in Medicinal Chemistry