title: Exploratory toxicology as an integrated part of drug discovery. Part I: Why and how.
abstract: Toxicity and clinical safety have major impact on drug development success. Moving toxicological studies into earlier phases of the R&D chain prevents drug candidates with a safety risk from entering clinical development. However, to identify candidates without such risk, safety has to be designed actively. Therefore, we argue that toxicology should be fully integrated into the discovery process. We describe our strategy, including safety assessment of novel targets, selection of chemical series without inherent liabilities, designing out risk factors and profiling of candidates, and we discuss considerations regarding what to screen for. We aim to provide timely go/no-go decisions (fail early) and direction to the discovery teams, by steering away from safety risk (showing what will not fail).
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; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D012449:Safety