A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity.

ABSTRACT: Assessing the potential of a new drug to cause drug-induced liver injury (DILI) is a challenge for the pharmaceutical industry. We therefore determined whether cell models currently used in safety assessment (HepG2, HepaRG, Upcyte and primary human hepatocytes in conjunction with basic but commonly used endpoints) are actually able to distinguish between novel chemical entities (NCEs) with respect to their potential to cause DILI. A panel of thirteen compounds (nine DILI implicated and four non-DILI implicated in man) were selected for our study, which was conducted, for the first time, across multiple laboratories. None of the cell models could distinguish faithfully between DILI and non-DILI compounds. Only when nominal in vitro concentrations were adjusted for in vivo exposure levels we

SUBMITTER: Sison-Young RL 

PROVIDER: S-EPMC5316403 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature