Development of a hierarchical support vector regression-based in silico model for Caco-2 permeability

Abstract

Drug absorption is one of the critical factors that should be taken into account in the process of drug discovery and development. The human colon carcinoma cell layer (Caco-2) model has been frequently used as a surrogate to preliminarily investigate the intestinal absorption. In this study, a quantitative structure–activity relationship (QSAR) model was generated using the innovative machine learning-based hierarchical support vector regression (HSVR) scheme to depict the exceedingly confounding passive diffusion and transporter-mediated active transport. The HSVR model displayed good agreement with the experimental values of the training samples, test samples, and outlier samples. The predictivity of HSVR was further validated by a mock test and verified by various stringent statistical criteria. Consequently, this HSVR model can be employed to forecast the Caco-2 permeability to assist drug discovery and development.