Multidrug resistance protein 4 (MRP4 (also ABCC4))

Multidrug resistance protein 4 (MRP4, ABCC4) is an ATP-dependent unidirectional efflux transporter belonging to the C subfamily of the ATP-binding cassette (ABC) protein superfamily. It is broadly expressed in many human tissues including the brain, liver, kidney, and blood cells. MRP4 is responsible for exporting a wide variety of endogenous and xenobiotic organic anions—including drugs, drug metabolites, signaling molecules (cyclic nucleotides, prostanoids), bile acids, urate, and steroid conjugates—across cell membranes. It plays critical roles in protecting cells from toxic substances, modulating extracellular signaling pathways, and regulating tissue exposure to pharmaceuticals. MRP4 mediates the efflux of numerous clinically relevant drugs and contributes to the development of multidrug resistance in cancer. Inhibiting MRP4 can enhance the efficacy of certain chemotherapeutics but is challenging due to the lack of highly specific inhibitors[1][2][3][4][5][6].

Other names

ABCC4MOAT-BMOATBATP-binding cassette subfamily C member 4

Drugs are actively extruded from cells via ATP hydrolysis by MRP4, reducing their intracellular concentration and mediating multidrug resistance[5][2][3]. Inhibitors bind to the substrate binding pocket, directly competing with transport substrates and blocking efflux[4][2].