Reversal of P-glycoprotein-mediated MDR by 5,7,3',4',5'-pentamethoxyflavone and SAR.

Article Details

Citation

Choi CH, Kim JH, Kim SH

Reversal of P-glycoprotein-mediated MDR by 5,7,3',4',5'-pentamethoxyflavone and SAR.

Biochem Biophys Res Commun. 2004 Jul 30;320(3):672-9.

PubMed ID
15240100 [ View in PubMed
]
Abstract

During screening for the flavonoid chemosensitizers, it was found that 5,7,3',4',5'-pentamethoxyflavone (PMF) was equipotent to verapamil in vitro with respect to the chemosensitizing effect. PMF appears to have a chemosensitizing effect not only by increasing the intracellular accumulation of the drugs without competition in a binding site of azidopine but also by interfering with the substrate-stimulated ATPase activity. Structure-activity relationship suggests that methoxylated substitution and its numbers or sites of the rings are more important than its hydroxylated counterparts in chemosensitization. Overall, PMF is anticipated to be a novel and highly potent second-generation flavonoid chemosensitizer because PMF has significant advantages of having a high therapeutic index, of being a non-transportable inhibitor, and of having a low possibility of drug interactions at the azidopine-binding site of Pgp.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
QuercetinP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
QuercetinP-glycoprotein 1IC 50 (nM)52500N/AN/ADetails
VerapamilP-glycoprotein 1IC 50 (nM)400N/AN/ADetails