Investigation of BCRP-inhibitors using QSAR and machine learning methods

Abstract

BCRP is the second member of the subfamily G of the ABC transporters. BCRP is involved in several physiological functions, including protection of the human body from xenobiotics. The overexpression of this membrane protein in certain tumor cell lines leads to cross-resistance against various chemotherapeutic drugs. In this work, the inhibitory activity of several compounds against BCRP and P-gp were assayed using a Hoechst 33342 assay for BCRP and a Calcein AM assay for P-gp. Furthermore, the potency of the studied compounds has been rationalized using a classical QSAR approach. Finally, three machine learning algorithms (Self-Organizing Maps, Support Vector Machine and k-Nearest Neighbors) were used, in order to generate a global model useful to predict if small ligands could be (or not) BCRP-inhibitors.