Journal
DRUG DISCOVERY TODAY
Volume 19, Issue 8, Pages 1137-1144Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2013.12.009
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In an effort to reduce toxicity-related attrition, different strategies have been implemented throughout the pharmaceutical industry. Previously (in Part I), we have outlined our 'integrated toxicology' strategy, which aims to provide timely go/no-go decisions (fail early) but also to show a direction to the drug discovery teams (showing what will not fail). In this review (Part II of the series) we describe our compound testing strategies with respect to cardiovascular safety, hepatotoxicity, genotoxicity, immunotoxicity and exploratory in vivo toxicity. We discuss the in vitro, ex vivo and in vivo assays and models we employ to assess safety risks and optimize compound series during the drug discovery process, including their predictivity and the decisions they generate.
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