Multidrug resistance protein 1 (P-glycoprotein 1) (ABCB1)

Multidrug resistance protein 1 (P-glycoprotein 1), encoded by the ABCB1 gene, is a critical ATP-binding cassette (ABC) transporter that functions as an energy-dependent efflux pump (UniProt P08183). It is widely expressed in physiological barriers such as the intestinal epithelium, hepatocytes, renal proximal tubules, and the blood-brain barrier, where it limits the entry of xenobiotics and promotes their excretion (StatPearls NBK555932). P-glycoprotein (P-gp) has broad substrate specificity, transporting a diverse range of hydrophobic compounds including chemotherapeutics, immunosuppressants, and cardiac glycosides (PubMed 12130706). In oncology, the overexpression of P-gp is a primary driver of multidrug resistance, as it effectively lowers the intracellular concentration of anticancer drugs below therapeutic levels (PubMed 25406332). Beyond cancer, P-gp plays a significant role in drug-drug interactions, where inhibitors or inducers of the transporter can drastically alter the pharmacokinetics of co-administered medications (FDA Guidance). Therapeutic strategies often focus on inhibiting P-gp to improve drug bioavailability or overcome resistance, though this remains a challenge due to the transporter's essential protective roles in healthy tissues. The transporter's activity is also linked to neurological conditions, where its dysfunction at the blood-brain barrier can affect the clearance of metabolic byproducts like amyloid-beta (PubMed 20045957). Understanding P-gp's structure and function is vital for drug development to ensure safety and efficacy in polypharmacy scenarios.

Other names

P-glycoproteinP-gpATP-binding cassette sub-family B member 1CD243Permeability glycoproteinMDR1

Drugs interact with P-glycoprotein as substrates (transported out of the cell), inhibitors (blocking the efflux of other substrates), or inducers (increasing the expression and activity of the transporter) (PubMed 12130706).