Use In Silico and In Vitro Methods to Screen Hepatotoxic Chemicals and CYP450 Enzyme Inhibitors

Authors: Liu Y
Publication: Methods Mol Biol
Software: ADMET Predictor®


In silico and in vitro methods have emerged as valuable tools to rapidly screen and prioritize large numbers of chemicals including new drug entities, food ingredients, and environmental compounds for further in vivo analysis. These methods have been frequently used to conduct screening for a wide range of endpoints including physicochemical properties (e.g., logD), human biokinetic parameters (e.g., metabolism), and human organ toxicities (e.g., hepatotoxicity). This chapter describes a tiered approach of incorporating multiple in silico (quantitative structure–activity relationship, QSAR) and in vitro (e.g., human liver cell models, human liver microsomes) methods into the screening of hepatotoxic chemicals and cytochromes P450 enzyme (CYP) inhibitors. Chemicals are prioritized for further studies (e.g., in vivo animal study) based on the in silico and in vitro results, as well as a literature search for their in vivo exposures (e.g., plasma concentration).

By Yitong Liu