title: Exploratory toxicology as an integrated part of drug discovery. Part II: Screening strategies.
abstract: 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.
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Hornberg
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Laursen
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Brenden
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Mikael
authors.initials: M
authors.lastname: Persson
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Annemette V
authors.initials: AV
authors.lastname: Thougaard
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Dorthe B
authors.initials: DB
authors.lastname: Toft
authors.affiliation: Department of Exploratory Toxicology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: tmo@lundbeck.com.
authors.forename: Tomas
authors.initials: T
authors.lastname: Mow
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004345:Drug Industry / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D012449:Safety