Integrated Application of Enhanced Replacement Method and Ensemble Learning for the Prediction of BCRP/ABCG2 Substrates

Abstract

Background: Breast Cancer Resistance Protein (BCRP or ABCG2) is a polyspecific effluxtransporter which belongs to the ATP-binding Cassette superfamily. Up-regulation of BCRP is associated to multi-drug resistance in a number of conditions, e.g. cancer and epilepsy. Recent proteomic studies show that high expression levels of BCRP are found in healthy human intestine and at the blood-brain barrier, limiting the absorption and brain distribution of its substrates. Therefore, the early recognition of BCRP substrates seems to be crucial in the early phase of drug discovery. Keywords: Breast Cancer Resistance Protein, ABC transporters, ABCG2, enhanced replacement method, ensemble learning, linear classifiers.