Abstract
In this study we describe a method to identify important genes that appear to be involved in the cytotoxic mechanisms of key molecular fragments (biophores) contained within the structures of anticancer compounds. The anticancer biophores were mined by the MULTICASE program by analyzing 60 datasets containing 3271 compounds tested against the NCI-60 human cancer cell lines. For each identified fragment, statistically relevant genes were found by relating the activity profiles of the molecules containing the fragment and the gene expression profiles of the different cell lines. Microarray gene expression data of 13111 genes was used in conjunction with the LeFE algorithm to accomplish this task. We have demonstrated that regression analysis can then predict the cytotoxic activity of a compound in cell lines outside of those included in the regression model, even if it belongs to a different cancer type provided that the expression levels of identified genes are known for the cell lines. It is hoped that identifying key genes within the context of specific substructures responsible for the cytotoxic activity of anticancer agents could offer a better handle for designing specialized drugs targeting specific tumors based on their genetic profile.
Keywords: NCI-60, MULTICASE, anti-cancer, chemogenomics, cancer genes
Current Computer-Aided Drug Design
Title: Finding Relevant Genes Involved in the Cytotoxicity Mechanisms of Anticancer Biophores
Volume: 5 Issue: 4
Author(s): Suman K. Chakravarti and Gilles Klopman
Affiliation:
Keywords: NCI-60, MULTICASE, anti-cancer, chemogenomics, cancer genes
Abstract: In this study we describe a method to identify important genes that appear to be involved in the cytotoxic mechanisms of key molecular fragments (biophores) contained within the structures of anticancer compounds. The anticancer biophores were mined by the MULTICASE program by analyzing 60 datasets containing 3271 compounds tested against the NCI-60 human cancer cell lines. For each identified fragment, statistically relevant genes were found by relating the activity profiles of the molecules containing the fragment and the gene expression profiles of the different cell lines. Microarray gene expression data of 13111 genes was used in conjunction with the LeFE algorithm to accomplish this task. We have demonstrated that regression analysis can then predict the cytotoxic activity of a compound in cell lines outside of those included in the regression model, even if it belongs to a different cancer type provided that the expression levels of identified genes are known for the cell lines. It is hoped that identifying key genes within the context of specific substructures responsible for the cytotoxic activity of anticancer agents could offer a better handle for designing specialized drugs targeting specific tumors based on their genetic profile.
Export Options
About this article
Cite this article as:
Chakravarti K. Suman and Klopman Gilles, Finding Relevant Genes Involved in the Cytotoxicity Mechanisms of Anticancer Biophores, Current Computer-Aided Drug Design 2009; 5 (4) . https://dx.doi.org/10.2174/157340909789577883
DOI https://dx.doi.org/10.2174/157340909789577883 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
- 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
-
Intracellular ROS Generation Mediates Maleimide-induced Cytotoxicity in Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry Growth and Trophic Factors, pH and the Na+/H+ Exchanger in Alzheimers Disease, Other Neurodegenerative Diseases and Cancer: New Therapeutic Possibilities and Potential Dangers
Current Alzheimer Research Mechanisms to Inhibit Matrix Metalloproteinase Activity: Where are we in the Development of Clinically Relevant Inhibitors?
Recent Patents on Anti-Cancer Drug Discovery Crosstalk between IGF-1R and other Tumor Promoting Pathways
Current Pharmaceutical Design Immunotherapy of Kidney Cancer
Current Clinical Pharmacology In Vivo DNA Electrotransfer for Immunotherapy of Cancer and Neurodegenerative Diseases
Current Drug Metabolism What are the Cancer Risks in BRCA Carriers Apart from Those Regarding the Breast and the Ovary?
Current Women`s Health Reviews Design, Synthesis and Biological Evaluation of 4, 6-Coumarin Derivatives as Anti- Cancer and Apoptosis-Inducing Agents
Anti-Cancer Agents in Medicinal Chemistry Immunomodulatory Activity of Garlic
Current Immunology Reviews (Discontinued) Design of Peptide Imaging Agents for Whole-body and Intraoperative Molecular Imaging
Current Medicinal Chemistry The Role of Transmembrane Segment II in 7TM Receptor Activation
Current Molecular Pharmacology The Use of Interferons in Respiratory Diseases
Current Respiratory Medicine Reviews NMR-based Drug Development and Improvement Against Malignant Melanoma – Implications for the MIA Protein Family
Current Medicinal Chemistry How Inhaled Asbestos Causes Scarring and Cancer
Current Respiratory Medicine Reviews Peptide Nucleic Acids: A Novel Approach
Current Chemical Biology Tea (Camellia sinensis (L.)): A Putative Anticancer Agent in Bladder Carcinoma?
Anti-Cancer Agents in Medicinal Chemistry Chemical Constituents and Biological Activities of Vietnamese Medicinal Plants
Current Topics in Medicinal Chemistry Resveratrol: A Therapeutic Promise for Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Recent Advancement in Discovery and Development of Natural Product Combretastatin-inspired Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry CD133 Expressing Pericytes and Relationship to SDF-1 and CXCR4 in Spinal Cord Injury
Current Neurovascular Research