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Nat Rev Drug Discov. 2005 May;4(5):410-20.

Elucidating mechanisms of drug-induced toxicity.

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  • 1Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 23rd and Pierce Avenues, Nashville, Tennessee 37232-0146, USA.


The early and high-throughput application of assays for non-genetic toxicity is of great interest to the pharmaceutical industry, although few systems have been validated as being of good predictive value. New technologies could enable toxicity to be studied in the context of systems biology. An important factor to be considered is the metabolism of drugs to reactive intermediates. Chemical reactions of these with cell and tissue nucleophiles are relatively well understood, but predicting how biological modifications will affect signalling and regulatory networks remains a challenge. Some of these pathways could be useful as sentinels for toxicity. This article will cover some examples of drug toxicity and the prospects for future technology development.

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