Abstract

Assessment of pharmacokinetic properties of compounds is a critical step in drug discovery. Measuring hepatic stability is essential in establishing the drug accumulation and clearance in the body. Usually, this endpoint is evaluated in vivo, using rats, or in vitro, using human liver microsomes. Recently, in silico approaches been recognized as alternative approaches to evaluating the pharmacokinetic properties of bioactive compounds. Herein, we describe (i) the collection, curation, and integration of the largest publicly available dataset of human hepatic stability measured in vitro with liver microsomes and (ii) the development and statistical validation of robust and predictive QSAR models for this endpoint. We collected, curated, and integrated the largest publicly available dataset for human hepatic stability and developed robust and predictive QSAR models. These can be employed to predict the half-life of compounds in human liver microsomes with high accuracy. The models will be implemented as part of a comprehensive platform for the prediction of pharmacokinetic parameters, which will be freely available for the scientific community.