P-glycoprotein (ABCB1) (P-gp or MDR1)

P-glycoprotein is a well-characterized ATP-dependent efflux transporter belonging to the ATP-binding cassette (ABC) family. Encoded by the ABCB1 gene (also known as MDR1), it is a 170 kDa transmembrane protein that exports a wide range of hydrophobic compounds—including many drugs—out of cells. It plays critical physiological roles in protecting tissues such as the brain, liver, kidney, intestines, testis, and placenta from toxic xenobiotics and endogenous metabolites. In cancer cells, overexpression leads to multidrug resistance by reducing intracellular concentrations of chemotherapeutic agents. The protein forms part of key biological barriers like the blood-brain barrier and influences both drug bioavailability and elimination. Its broad substrate specificity arises from large flexible binding pockets within its transmembrane domains that accommodate multiple molecules simultaneously. Clinical interest centers on overcoming its role in therapy resistance through selective inhibitors or modulators.

Other names

Multidrug resistance protein 1MDR1ABCB1Pgp

Drugs targeting P-glycoprotein act primarily by one or more of the following mechanisms: - Inhibition of efflux activity to increase intracellular drug concentration (e.g., verapamil as an inhibitor) - Modulation/induction to alter transporter expression or function Chemotherapeutic agents are often substrates; their efficacy is reduced when actively exported by P-gp.