title: Model-based drug discovery: implementation and impact.
abstract: Model-based drug discovery (MBDDx) aims to build and continuously improve the quantitative understanding of the relation between drug exposure (target engagement) efficacy and safety, to support target validation; to define compound property criteria for lead optimization and safety margins; to set the starting dose; and to predict human dose and scheduling for clinical candidates alone, or in combination with other medicines. AstraZeneca has systematically implemented MBDDx within all drug discovery programs, with a focused investment to build a preclinical modeling and simulation capability and an in vivo information platform and architecture, the implementation, impact and learning of which are discussed here.
authors.affiliation: Global Drug Metabolism and Pharmacokinetics, Innovative Medicines, AstraZeneca, Södertälje, Sweden.
authors.forename: Sandra A G
authors.initials: SA
authors.lastname: Visser
authors.forename: Malin
authors.initials: M
authors.lastname: Aurell
authors.forename: Rhys D O
authors.initials: RD
authors.lastname: Jones
authors.forename: Virna J A
authors.initials: VJ
authors.lastname: Schuck
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Egnell
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Peters
authors.forename: Lena
authors.initials: L
authors.lastname: Brynne
authors.forename: James W T
authors.initials: JW
authors.lastname: Yates
authors.forename: Rasmus
authors.initials: R
authors.lastname: Jansson-Löfmark
authors.forename: Beesan
authors.initials: B
authors.lastname: Tan
authors.forename: Marie
authors.initials: M
authors.lastname: Cooke
authors.forename: Simon T
authors.initials: ST
authors.lastname: Barry
authors.forename: Andrew
authors.initials: A
authors.lastname: Hughes
authors.forename: Ulf
authors.initials: U
authors.lastname: Bredberg
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000639:trends; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations