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FEBS Lett. 2008 Apr 9;582(8):1276-82. doi: 10.1016/j.febslet.2008.01.063. Epub 2008 Feb 20.

Multiple effects of acetaminophen and p38 inhibitors: towards pathway toxicology.

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  • 1Systems Biology, Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, United States. jim.xu@pfizer.com


The majority of drug-related toxicities are idiosyncratic, with little pathophysiological insight and mechanistic understanding. Pathway toxicology is an emerging field of toxicology in the post-genomic era that studies the molecular interactions between toxicants and biological pathways as a way to bridge this knowledge gap. Using two case studies--acetaminophen and p38 MAPK inhibitors--this review illustrates how a pathway-based perspective has advanced our understanding of compound and target-based toxicities. The advancement of pathway toxicology will be dependent on integrated applications of techniques from basic sciences and a fundamental understanding of the interdependence of multiple biological pathways in living organisms.

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