P-glycoprotein and Multidrug resistance-associated protein 1 (P-gp/MRP1)

P-glycoprotein (P-gp, MDR1, ABCB1) and multidrug resistance-associated protein 1 (MRP1, ABCC1) are ATP-binding cassette (ABC) transporters that function as membrane efflux pumps for a wide range of structurally unrelated drugs and xenobiotics. They play a key physiological role in protecting tissues by exporting toxins back into extracellular spaces such as the intestinal lumen, bile, urine, and protective barriers (blood-brain, blood-testis). In cancer, overexpression of P-gp or MRP1 is a principal mechanism underlying multidrug resistance, as these proteins actively transport chemotherapeutics out of cancer cells, reducing their effectiveness. Both transporters are targets for drug development aimed at overcoming resistance, and a wide array of both substrate drugs and inhibitors have been identified. Their activity also affects drug pharmacokinetics in normal tissues and can influence the risk of drug–drug interactions, toxicity, and therapeutic failure

Other names

Permeability glycoproteinMDR1ABCB1Cluster of differentiation 243 (CD243)PgpABCC1Multidrug resistance protein 1

ATP-dependent efflux of drugs and xenobiotics from cells, decreasing intracellular drug concentration Facilitation of multidrug resistance by preventing cytotoxic drug accumulation Inhibition: Blockade of transporter function increases sensitivity of cancer cells to chemotherapy