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Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism

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Title: Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism
Authors: Stahl, SH
Yates, JW
Nicholls, AW
Kenna, JG
Coen, M
Ortega, F
Nicholson, JK
Wilson, ID
Item Type: Journal Article
Abstract: © 2015 Elsevier Ltd. All rights reserved.One aim of systems toxicology is to deliver mechanistic, mathematically rigorous, models integrating biochemical and pharmacological processes that result in toxicity to enhance the assessment of the risk posed to humans by drugs and other xenobiotics. The benefits of such in silico models would be in enabling the rapid and robust prediction of the effects of compounds over a range of exposures, improving in vitro-in vivo correlations and the translation from preclinical species to humans. Systems toxicology models of organ toxicities that result in high attrition rates during drug discovery and development, or post-marketing withdrawals (e.g., drug-induced liver injury (Dili)) should facilitate the discovery of safe new drugs. Here, systems toxicology as applied to the effects of paracetamol (acetaminophen, N-acetyl-para-aminophenol (APAP)) is used to exemplify the potential of the approach.
Issue Date: 16-Jul-2015
Date of Acceptance: 16-Jul-2015
URI: http://hdl.handle.net/10044/1/26499
DOI: https://dx.doi.org/10.1016/j.ddtec.2015.06.003
ISSN: 1740-6749
Publisher: Elsevier
Start Page: 9
End Page: 14
Journal / Book Title: Drug Discovery Today: Technologies
Volume: 15
Copyright Statement: © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer