The kinetics of drug interactions between modulators and substrates on P-gp
Drug (n > 3) | [3H]Vinblastine | [3H]XR9576 | ||||
---|---|---|---|---|---|---|
Maximal k−1 | Fold Change | EC50 | Maximal k−1 | Fold Change | EC50 | |
min−1 | μM | min−1 | nM | |||
Vinblastine | 0.093 | |||||
XR9576 | 0.493 | 5.3 | 0.456 | 0.0230 | ||
XR9000 | 0.293 | 3.2 | 0.170 | 0.0315 | 1.4 | 78 |
Nicardipine | 0.452 | 4.9 | 1.2 | 0.0494 | 1.5 | 1700 |
XR9051 | 0.370 | 4 | 0.29 | |||
Paclitaxel | 0.114 | 1.2 | 0.024 | |||
Hoechst 33342 | 0.317 | 3.4 | 18 |
The dissociation rate constants for the outlined compounds on the binding of either [3H]vinblastine or [3H]XR9576 were determined as described under Experimental Procedures. The dissociation rates were determined at a number of drug concentrations and the maximal rate constant (k−1) was estimated from nonlinear regression of the general dose-response equation. The potency of each compound to increase the dissociation rate constant for radioligand is shown as an EC50 value.