title: Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy.
abstract: In this article, we review the past applications of in vitro models in identifying human hepatotoxins and then focus on the use of multiscale experimental models in drug development, including the use of zebrafish and human cell-based, 3-dimensional, microfluidic systems of liver functions as key components in applying Quantitative Systems Pharmacology (QSP). We have implemented QSP as a platform to improve the rate of success in the process of drug discovery and development of therapeutics.
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh Drug Discovery Institute, Biomedical Science Tower 200 Lothrop Street, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: vernetti@pitt.edu.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Vernetti
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh Drug Discovery Institute, Biomedical Science Tower 200 Lothrop Street, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vogt
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh Drug Discovery Institute, Biomedical Science Tower 200 Lothrop Street, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Gough
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh Drug Discovery Institute, Biomedical Science Tower 200 Lothrop Street, University of Pittsburgh, Pittsburgh, PA 15260, USA; University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, USA.
authors.forename: D Lansing
authors.initials: DL
authors.lastname: Taylor
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019418:Evolution, Chemical; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008322:Mammals; D023421:Models, Animal; D011237:Predictive Value of Tests; D018570:Risk Assessment
keywords: Drug discovery; Drug-induced liver injury; Human liver models; In vitro hepatotoxicity; Liver toxicology; Microphysiology liver; Quantitative system pharmacology