Quantitative Structure-Activity Relationship (QSAR) Analysis to Predict Drug-Drug Interactions of ABC Transporter ABCG2

T.      Ishikawa; H.      Hirano; H.      Saito; K.      Sano; Y.      Ikegami; N.      Yamaotsu; S.      Hirono

doi:10.2174/138955712800493825

Abstract

Quantitative structure-activity relationship (QSAR) analysis is a practical approach by which chemical structure is quantitatively correlated with biological activity or chemical reactivity. Human ABC transporter ABCG2 exhibits broad substrate specificity toward structurally diverse compounds. To gain insight into the relationship between the molecular structures of compounds and the interaction with ABCG2, we have developed an algorithm that analyzes QSAR to evaluate ABCG2-drug interactions. In addition, to support QSAR analysis, we developed a high-speed screening method for analyzing the drug-drug interactions of ABCG2. Based on both experimental results and computational QSAR analysis data, we propose a hypothetical mechanism underlying ABC-mediated drug transport and its interaction with drugs.

Keywords: ABC transporter, ABCG2, camptothecin, gefitinb, irinotecan, multidrug resistance, QSAR analysis, ATP-γ-S, doxorubicin-resistant, Cys592, Cys608, cysteinyl disulfide, aliquots