Unraveling Mechanisms of Toxicity with the Power of Pathways: ToxWiz Tool as an Illustrative Example
Mark Kühnel, Bojana Cosovic, Goran Medić, Robert B. Russell, Gordana Apic · 2008
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