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Abstract
The pharmaceutical industry has begun to leverage a range of new technologies (proteomics, pharmacogenomics, metabolomics and molecular toxicology [e.g., toxicogenomics]) and analysis tools that are becoming increasingly integrated in the area of drug discovery and development. The approach of analyzing the vast amount of toxicogenomics data generated using molecular pathway and networks analysis tools in combination with analysis of reference data will be the main focus of this review. We will demonstrate how this combined approach can increase the understanding of the molecular mechanisms that lead to chemical-induced toxicity and application of this knowledge to compound risk assessment. We will provide an example of the insights achieved through a molecular toxicology analysis based on the well-known hepatotoxicant lipopolysaccharide to illustrate the utility of these new tools in the analysis of complex data sets, both in vivo and in vitro. The ultimate objective is a better lead selection process that improves the chances for success across the different stages of drug discovery and development.
Acknowledgements
The authors would like to thank Craig Giroux (Karmanos Cancer Institute, Wayne State University, Don Halbert (Iconix Biosciences), Megan Laurence and Dana Abramovitz (Ingenuity Systems) for critical reading of the manuscript.
Financial and competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.