Multidrug resistance protein 1 (MDR1) (MDR1)

Multidrug resistance protein 1 (MDR1), commonly known as P-glycoprotein (P-gp), is a 170 kDa transmembrane phosphoglycoprotein that functions as an ATP-dependent efflux pump within the ATP-binding cassette (ABC) transporter family [PMID: 11560815]. In lymphocytes, P-gp is expressed on various subsets including T-cells, B-cells, and Natural Killer (NK) cells, where it facilitates the transport of endogenous molecules like cytokines (e.g., IL-2, IFN-gamma) and protects cells from toxic xenobiotics [PMID: 22430123]. The overexpression of P-gp on lymphocytes is a major mechanism of multidrug resistance (MDR), as it actively extrudes a wide range of structurally diverse therapeutic agents, such as corticosteroids and chemotherapeutics, from the intracellular environment [PMID: 15652226]. This overexpression is frequently observed in patients with refractory autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, as well as in hematological malignancies like chronic lymphocytic leukemia, leading to poor treatment outcomes [PMID: 12130547]. Pharmacological strategies targeting P-gp involve the use of inhibitors or chemosensitizers to block efflux activity and restore drug sensitivity; however, these interventions must be carefully managed due to P-gp's essential role in maintaining the blood-brain barrier and influencing the pharmacokinetics of numerous co-administered drugs [PMID: 11560815].

Other names

P-glycoproteinP-gpABCB1ATP-binding cassette sub-family B member 1CD243P-glycoprotein 1

Inhibition of ATP-dependent efflux activity to increase intracellular drug concentration and restore sensitivity to therapeutic substrates.