Reversal of P-glycoprotein-mediated MDR by 5,7,3',4',5'-pentamethoxyflavone and SAR.
Article Details
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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
Drug Transporter Kind Organism Pharmacological Action Actions Quercetin P-glycoprotein 1 Protein Humans UnknownInhibitorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Quercetin P-glycoprotein 1 IC 50 (nM) 52500 N/A N/A Details Verapamil P-glycoprotein 1 IC 50 (nM) 400 N/A N/A Details