Drug Discov Ther. 2008;2(6):305-332.

Role of multidrug resistance associated proteins in drug development.

Zhou SF


The multidrug resistance associated proteins (MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8 and MRP9) belongs to the ATP-binding cassette superfamily (ABCC family) of transporters expressed differentially in the liver, kidney, intestine and blood-brain barrier. MRPs transport a structurally diverse array of endo- and xenobiotics and their metabolites (in particular conjugates) and are subject to induction and inhibition by a variety of compounds. An increased efflux of natural product anticancer drugs and other anticancer agents by MRPs in cancer cells is associated with tumor resistance. These transporting proteins play a role in the absorption, distribution and elimination of various compounds in the body. There are increased reports on the clinical impact of genetic mutations of genes encoding MRP1-9. Therefore, MRPs have an important role in drug development, and a better understanding of their function and regulating mechanism can help minimize and avoid drug toxicity, unfavourable drug-drug interactions, and to overcome drug resistance.

KEYWORDS: MRP, Drug development, Single nucleotide polymorphism, Toxicity, Pharmacokinetics, Blood-brain barrier, Biliary excretion, Intestinal absorption, Drug transport

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