title: Assessment of P-glycoprotein substrate and inhibition potential of test compounds in MDR1-transfected MDCK cells.
abstract: P-glycoprotein (P-gp) is the most widely studied drug transporter due to its potential role in drug disposition and efficacy, and drug-drug interactions (DDI). It is abundantly expressed in both the intestinal wall and blood-brain barrier where it serves as a drug permeability barrier while simultaneously facilitating drug elimination in the liver and kidney. It is also abundantly expressed in tumors where it can facilitate the elimination of chemotherapeutics, a phenomenon known as multidrug resistance (MDR). Clinically relevant DDIs involving P-gp are well documented; for example, the P-gp substrate, digoxin, exhibits toxicity when co-administered with a Pgp-inhibitor. This makes it essential to screen new chemical entities early in development for their potential to be a substrate and/or inhibitor of P-gp. Detailed in this unit is an in vitro protocol for assessing the P-gp substrate and inhibition potential of test compounds using the MDCK MDR1 and MDCK WT cell lines.
authors.affiliation: NoAb BioDiscoveries, Mississauga, Ontario, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: C L Lam
authors.forename: Ganesh
authors.initials: G
authors.lastname: Rajaraman
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D001681:Biological Assay / Q000379:methods; D018929:Cell Culture Techniques; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D004347:Drug Interactions / Q000502:physiology*; D018432:Drug Resistance, Multiple / Q000502:physiology; D017097:Electric Impedance; D019450:Genes, MDR; D006801:Humans; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations