Application of cellular membrane affinity chromatography in determining stereoselective interactions with ATP-binding cassette transporters

The ATP-binding cassette (ABC) efflux transporters plays a key role in drug absorption and excretion hence the determination of a compound's interaction with these transporters becomes a key element in drug discovery programs. ABC transporters also play a role in multiple drug resistance (MDR), a common obstacle in chemotherapeutic management of most neoplastic tumours as well as a number of other diseases such as malaria and tuberculosis. While there are a variety of approaches to the determination of drug interactions with ABC transporters, the direct measurement of stereoselective interactions remains a difficult task. In this review we address this issue and demonstrate that cellular membrane affinity chromatography (CMAC) utilizing columns containing immobilized ABC transporters can be used as a direct online method for the determination of stereoselective small molecule-drug transporter interactions. The CMAC columns discussed in this work contain the ABC transporter P-glycoprotein; the CMAC (Pgp) column, multiple drug resistant protein 1; the CMAC (MRP1) column, multiple drug resistance protein 2; the CMAC (MRP2) column and breast cancer resistant protein; the CMAC (BCRP) column.