Mechanism-based drug safety testing using innovative in vitro liver models: from DILI prediction to idiosyncratic DILI liability assessment

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: June 5, 2025

Idiosyncratic drug-induced liver injury (iDILI) remains unpredictable. As adverse responses arise in a small fraction of patients, drugs often fail later drug development stages or post-approval, thereby tremendously increasing costs and putting patients at risk, highlighting the need for accurate early identification iDILI liabilities. Using articles from last five years (PubMed), risk factors are described, vitro models mechanism-based readout strategies evaluated on their potential to enable liability assessment. Various established disease modeling DILI prediction. Drawbacks each these seem inevitable, making evaluation application domain assessment crucial. A tiered approach could be considered, whereby compounds initially screened flagged using simple fit-for-purpose prediction, followed by multicellular that integrate current knowledge onset combination with mechanistic readouts. Multiplexing within an integrated testing strategy improve safety accuracy. Defined should critical hepatocyte intrinsic as well adaptive immune system components refine

Language: Английский

Four functional genotoxic marker genes (Bax, Btg2, Ccng1, and Cdkn1a) discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens and non-genotoxic non-hepatocarcinogens in rat public toxicogenomics data, Open TG-GATEs

Genes and Environment, Journal Year: 2024, Volume and Issue: 46(1)

Published: Dec. 19, 2024

Language: Английский