Integrating Drug's Mode of Action into Quantitative Structure-Activity Relationships for Improved Prediction of Drug-Induced Liver Injury.

ABSTRACT: Drug-induced liver injury (DILI) is complex in mechanism. Different drugs could undergo different mechanisms but result in the same DILI type, while the same drug could lead to different DILI types via different mechanisms. Therefore, predicting a drug's potential for DILI should take its underlying mechanisms into consideration. To achieve that, we constructed a novel approach by incorporating the drug's Mode of Action (MOA) into Quantitative Structure-Activity Relationship (QSAR) modeling. This MOA-DILI approach was examined using a data set of 333 drugs. The drugs were first grouped according to their MOA profiles (positive or negative in each MOA) based on the Tox21 qHTS assays. QSAR models for individual MOA assays were developed and subsequently combined to obtain the MOA-DILI model.

SUBMITTER: Wu L 

PROVIDER: S-EPMC6233892 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature