PSC833, cyclosporin A, and dexniguldipine effects on cellular calcein retention and inhibition of the multidrug resistance pump in human leukemic lymphoblasts.

Article Details

Citation

Copy to clipboard

Wigler PW

PSC833, cyclosporin A, and dexniguldipine effects on cellular calcein retention and inhibition of the multidrug resistance pump in human leukemic lymphoblasts.

Biochem Biophys Res Commun. 1999 Apr 13;257(2):410-3.

PubMed ID

10198227 [ View in PubMed

]

Abstract

A convenient functional assay of the multidrug resistance (MDR) pump is useful for the diagnosis of MDR-1 cancers and the quantitative determination of the potency of inhibitors of the pump. Calcein-AM, a substrate of the MDR pump, was used to determine the concentration of SDZ PSC833 needed to completely inhibit the pump in CEM/VLB100 drug-resistant cells. The initial rates (in percent) for calcein retention by these MDR-1 cells were used to calculate values for the percent initial efflux of calcein-AM through the MDR pump in the presence of the inhibitors PSC833, cyclosporinA, and dexniguldipine. The percent efflux values at 250 and 60 nM calcein-AM were used to calculate the required concentration of each inhibitor to produce half-inhibition (I50) of initial efflux through the pump. These results are consistent with a noncompetitive inhibition of the MDR pump by each of the three inhibitors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cyclosporine	P-glycoprotein 1	Ki (nM)	1800	N/A	N/A	Details