Chapter 9. Unraveling Mechanisms of Toxicity with the Power of Pathways: ToxWiz Tool as an Illustrative Example

  1. Anton Yuryev PhD
  1. Mark P. Kühnel1,
  2. Bojana Cosovic2,
  3. Goran Medic2,
  4. Robert B. Russell3 and
  5. Gordana Apic2

Published Online: 21 APR 2008

DOI: 10.1002/9780470399279.ch9

Pathway Analysis for Drug Discovery: Computational Infrastructure and Applications

Pathway Analysis for Drug Discovery: Computational Infrastructure and Applications

How to Cite

Kühnel, M. P., Cosovic, B., Medic, G., Russell, R. B. and Apic, G. (2008) Unraveling Mechanisms of Toxicity with the Power of Pathways: ToxWiz Tool as an Illustrative Example, in Pathway Analysis for Drug Discovery: Computational Infrastructure and Applications (ed A. Yuryev), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/9780470399279.ch9

Editor Information

  1. Ariadne Genomics Inc., 9430 Key West Avenue, Suite 113, Rockville, MD 20850, USA

Author Information

  1. 1

    EMBL-Heidelberg, Cell Biology and Biocomputing Meyerhofstrasse 1, 69117 Heidelberg, Germany

  2. 2

    Cambridge Cell Networks Ltd, St John's Innovation Centre, Cowley Road, CB4 0WS Cambridge, United Kingdom

  3. 3

    EMBL-Heidelberg Biocomputing Meyerhofstrasse, 169117 Heidelberg, Germany

Publication History

  1. Published Online: 21 APR 2008
  2. Published Print: 12 SEP 2008

Book Series:

  1. Wiley Series on Technologies for the Pharmaceutical Industry

Book Series Editors:

  1. Sean Ekins

ISBN Information

Print ISBN: 9780470107058

Online ISBN: 9780470399279

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Keywords:

  • ToxWiz knowledge bases and toxic effects pathways;
  • systems biology approach in molecular toxicology mechanism;
  • phthalic compound chemical substructure search

Summary

This chapter contains sections titled:

  • Introduction

  • The Wind of Change in Toxicology: Toward Understanding Mechanisms of Toxicity and Predicting Toxicities for Novel Compounds

  • Systems Biology Approach Enables Unprecedented Insights into Molecular Mechanisms of Toxicology

  • Why Now and Not 30 Years Ago?

  • Predicting Toxicity and Making a Mechanistic Hypothesis Based Only on Chemical Structure: A Case Study with a Phthalates

  • Chemical Structure Search: Searching for Phthalate Compounds

  • Finding Toxicity in Testis by Analyzing Expression Study of Liver Tissue from Mice Treated with Phthalic Acid

  • Mapping the Microarray Data onto Toxic Endpoints

  • Exploring Toxic Endpoints

  • Combining the Results of the Substructure Search with the Microarray Data

  • Solution to Common Problems Toxicologists Face: Finding a Molecular Rationale for Unexpected Toxic Endpoints

  • Chemical Search for Nicotinate

  • Mapping the Compound Set onto Toxic Endpoints

  • Previously Observed Xenobiotics that Cause Testis Problems

  • Nicotinates with Lipophilic Substituents Acting on RARα

  • The Molecular Details of the Prediction

  • Exploring the Molecular Basis of Combination Drugs Using ToxWiz

  • Conclusions

  • About Cambridge Cell Networks

  • References