Exploratory toxicology as an integrated part of drug discovery. Part II: Screening strategies

•Toxicology has to be integrated in the drug discovery process to identify candidates with a superior safety profile.•We describe our screening strategy around a core battery of safety assays, models and studies.•Focus is on cardiovascular safety, hepatotoxicity, genotoxicity, immunotoxicity and general in vivo toxicity.•We aim to detect safety liabilities early and optimize compound series on safety. 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.