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

P-glycoprotein (P-gp), encoded by the ABCB1 gene, and Multidrug resistance-associated protein 1 (MRP1), encoded by the ABCC1 gene, are integral membrane proteins belonging to the ATP-binding cassette (ABC) transporter superfamily (UniProt P08183, P33527). These transporters utilize the energy of ATP hydrolysis to export a broad spectrum of chemically unrelated compounds, including various chemotherapeutic agents, from the cytoplasm to the extracellular space (PubMed: 25048911). Their primary biological role is to protect cells from xenobiotic toxicity and maintain physiological barriers, such as the blood-brain and blood-placental barriers (NIH: StatPearls). In clinical oncology, the overexpression of P-gp and MRP1 is a major driver of multidrug resistance (MDR), leading to the failure of chemotherapy in various cancers by preventing drugs from reaching therapeutic concentrations within tumor cells (PubMed: 30553482). While several generations of inhibitors, such as Tariquidar and Elacridar, have been developed to reverse MDR, their clinical utility has been limited by significant safety concerns, including the disruption of normal tissue protection and complex drug-drug interactions (PubMed: 23633442).

Other names

P-glycoproteinMDR1ABCB1ABCC1ATP-binding cassette sub-family B member 1ATP-binding cassette sub-family C member 1Multidrug resistance-associated protein 1

ATP-dependent efflux of substrate molecules across the cell membrane against a concentration gradient, reducing intracellular drug accumulation.