Multidrug resistance proteins (MRPs) and implication in drug development

Abstract

The multidrug resistance protein (MRP)-related ABCC family (MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, and MRP9) belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. They are capable of transporting a structurally diverse array of endo- and xenobiotics and their metabolites across cell membranes. These transporters play an important role in the absorption, disposition, and elimination of these compounds in the body. In particular, increased expression of these drug transporters in tumor cells is associated with resistance to a number of important chemotherapeutic agents. This review highlights the biochemical and pharmacological properties of MRP1-9 and their implications in drug development. A detailed study on the biochemical function and regulation of MRPs is important in drug development, as this may help to avoid drug toxicity, drug resistance, and drug-drug interactions and to optimize cancer chemotherapy. © 2005 Wiley-Liss, Inc.