Multidrug resistance-associated protein (MRP (or specific family members, e.g., MRP1, MRP2))

Multidrug resistance-associated proteins are a family of membrane-bound transporters belonging to the ATP-binding cassette (ABC) superfamily. They actively export a wide range of structurally diverse compounds—including anticancer drugs, antivirals, antibiotics, organic anions, and conjugated metabolites—out of cells using energy derived from ATP hydrolysis. These proteins play a major role in protecting tissues from toxic substances but also contribute significantly to clinical multidrug resistance by reducing intracellular concentrations of therapeutic agents. Key members include MRP1 (ABCC1), which is widely expressed and confers broad-spectrum drug resistance; MRP2 (ABCC2), critical for biliary excretion in hepatocytes; and others with specialized roles in different tissues. Overexpression is frequently observed in tumors resistant to chemotherapy as well as certain viral infections treated with nucleoside analogues. Genetic defects can result in metabolic disorders such as Dubin–Johnson syndrome due to impaired bilirubin clearance.

Other names

Multidrug resistance transporter proteinATP-binding cassette sub-family C member (e.g., ABCC1 for MRP1, ABCC2 for MRP2)Canalicular multispecific organic anion transporter 1 (for MRP2)cMOAT

Drugs targeting MRPs typically act by inhibiting the transporter's ability to efflux drugs from cells or by being substrates that are extruded from the cell. This reduces intracellular drug accumulation and leads to multidrug resistance in cancer and infectious disease therapy. Some inhibitors block the ATPase activity required for substrate transport.