Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy

Lawrence A Vernetti; Andreas Vogt; Albert Gough; D Lansing Taylor

doi:10.1016/j.cld.2016.08.013

Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy

Clin Liver Dis. 2017 Feb;21(1):197-214. doi: 10.1016/j.cld.2016.08.013.

Authors

Lawrence A Vernetti¹, Andreas Vogt², Albert Gough², D Lansing Taylor³

Affiliations

¹ 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.
² 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.
³ 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.

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.

Keywords: Drug discovery; Drug-induced liver injury; Human liver models; In vitro hepatotoxicity; Liver toxicology; Microphysiology liver; Quantitative system pharmacology.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Animals
Chemical and Drug Induced Liver Injury / prevention & control*
Drug Design*
Drug Discovery
Drug Evaluation, Preclinical / methods*
Evolution, Chemical
Humans
Liver / drug effects*
Mammals
Models, Animal
Predictive Value of Tests
Risk Assessment

Abstract

Publication types

MeSH terms

Grants and funding