Development of a fluorescence liposomal ABCG2 Multidrug Transporter assay

ABSTRACT In this project we propose to exploit the recent successful isolation and reconstitution of the important ATP- dependent drug efflux transporter, ABCG2 (BCRP, Breast Cancer Resistance Protein), and combine it with a new transport assay system, the Fluorosome platform, to characterize the interaction of ABCG2 with drugs and drug candidates. The result will provide a useful, novel, highly specific and rapid in vitro transport assay for future general use. We shall employ this assay together with ATPase studies to characterize a wide variety of ABCG2 substrates and modulators. Additionally, by means of this unique construct we shall screen the 89 anticancer drugs in the NCI Oncology Drug Set Plate series for inhibition of ABCG2-mediated transport. The ABCG2 protein is a ubiquitous high capacity drug transporter with wide substrate specificity. The White Paper recently issued by the International Transporter Consortium formed to propose industry and FDA standards for studies of drug:transporter inte