Pglikoprotein

P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) transporter that acts as an energy-dependent efflux pump for a wide range of hydrophobic compounds. It was identified as a major mediator of multidrug resistance in cancer cells and remains a key determinant of drug disposition in humans.

In humans, P-glycoprotein is encoded by the ABCB1 gene (also known as MDR1). The protein has two homologous halves, each containing six transmembrane helices and a nucleotide-binding domain. Together these domains form a transmembrane chamber that binds substrates and couples transport to ATP hydrolysis.

P-gp is expressed at the apical membranes of intestinal epithelial cells, hepatocytes, renal proximal tubule cells, and the endothelial cells of the blood-brain barrier, as well as in the placenta. By actively exporting substrates out of cells, it reduces intracellular drug accumulation, influences oral absorption and brain exposure, and promotes excretion into bile and urine.

Its substrates are chemically diverse, including chemotherapeutic agents (e.g., doxorubicin, paclitaxel), antibiotics, steroids, and many other drugs. Inhibitors and modulators of P-gp (for example, verapamil, cyclosporine A, tariquidar) have been explored to overcome resistance and alter pharmacokinetics, but clinical use is limited by toxicity and complex drug interactions. Genetic polymorphisms in ABCB1 can alter expression or function and contribute to interindividual variability in drug response.

P-glycoprotein remains a central focus in pharmacology and cancer biology because of its critical role in drug transport, resistance phenomena, and the pharmacokinetic behavior of numerous therapeutics.