Predicting Drug-Induced Cholestasis with the Help of Hepatic Transporters-An in Silico Modeling Approach.

ABSTRACT: Cholestasis represents one out of three types of drug induced liver injury (DILI), which comprises a major challenge in drug development. In this study we applied a two-class classification scheme based on k-nearest neighbors in order to predict cholestasis, using a set of 93 two-dimensional (2D) physicochemical descriptors and predictions of selected hepatic transporters' inhibition (BSEP, BCRP, P-gp, OATP1B1, and OATP1B3). In order to assess the potential contribution of transporter inhibition, we compared whether the inclusion of the transporters' inhibition predictions contributes to a significant increase in model performance in comparison to the plain use of the 93 2D physicochemical descriptors. Our findings were in agreement with literature findings, indicating a contribution not o

SUBMITTER: Kotsampasakou E 

PROVIDER: S-EPMC5411109 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature