Xenobiotic transporters

Xenobiotic transporters are a diverse group of membrane-bound proteins, primarily belonging to the ATP-binding cassette (ABC) and solute carrier (SLC) superfamilies, that regulate the movement of foreign compounds across cellular membranes. They play a critical role in the Phase III of drug metabolism by facilitating the absorption, distribution, and excretion of drugs and toxins (Klaassen, 2002). These transporters are strategically expressed in barrier tissues such as the intestine, liver, kidney, and blood-brain barrier, where they protect the body from toxic insults and maintain internal homeostasis (NIH, 2018). In clinical oncology, the overexpression of efflux transporters like P-glycoprotein is a major cause of multidrug resistance, as they actively pump chemotherapeutic agents out of cancer cells (Wikipedia, 2024). Conversely, inhibition or induction of these transporters by co-administered drugs can lead to significant drug-drug interactions, altering the safety and efficacy profiles of therapeutic regimens (Giacomini et al., 2010). Consequently, xenobiotic transporters are key focal points in drug discovery and regulatory safety assessments.

Other names

Drug transportersEfflux transportersUptake transportersPhase III biotransformation proteinsMembrane transporters

Drugs interact with xenobiotic transporters through competitive or non-competitive inhibition of substrate transport, or by inducing transporter expression via nuclear receptors such as the Pregnane X Receptor (PXR) and Constitutive Androstane Receptor (CAR).