Application of cellular membrane affinity chromatography in determining stereoselective interactions with ATP-binding cassette transporters
The ATP-binding cassette (ABC) efflux transportersplays a key role in drug absorption and excretion hencethe determination of a compound’s interaction with thesetransporters becomes a key element in drug discoveryprograms. ABC transporters also play a role in multiple drugresistance (MDR), a common obstacle in chemotherapeuticmanagement of most neoplastic tumours as well as a numberof other diseases such as malaria and tuberculosis. While thereare a variety of approaches to the determination of druginteractions with ABC transporters, the direct measurementof stereoselective interactions remains a difficult task. In thisreview we address this issue and demonstrate that cellularmembrane affinity chromatography (CMAC) utilizing columnscontaining immobilized ABC transporters can be used as adirect online method for the determination of stereoselectivesmall molecule-drug transporter interactions. The CMACcolumns discussed in this work contain the ABC transporterP-glycoprotein; the CMAC (Pgp) column, multiple drugresistant protein 1; the CMAC (MRP1) column, multiple drugresistance protein 2; the CMAC (MRP2) column and breastcancer resistant protein; the CMAC (BCRP) column.