Inhibition of efflux transporters by fluorescent bile acid derivatives
Transport experiments were performed as described in Material and Methods. The following substrates were used: BSEP 2 µM taurocholate and MRP2 10 µM estradiol 17β-d-glucuronide. Transport was measured for 5 minutes. Substrate uptake values in % were corrected for transport in the absence of ATP, and uptake in the absence of inhibitor was set to 100%. Results are the mean from two to four independent experiments with three technical replicates.
Compound | [I] | BSEP | MRP2 |
---|---|---|---|
µM | |||
CenNBD | 0 | 100 | 100 |
1 | 87.5 | 94.5 | |
10 | 46.0 | 124 | |
100 | 12.0 | 140 | |
CenDNS | 0 | 100 | 100 |
1 | 82.0 | 78.5 | |
10 | 50.5 | 106 | |
100 | 6.0 | 152 | |
CenPB | 0 | 100 | 100 |
1 | 80.0 | 94.5 | |
10 | 58.0 | 94.5 | |
100 | 16.5 | 91.0 | |
CDCenNBD | 0 | 100 | 100 |
1 | 67.5 | 122 | |
10 | 40.5 | 151 | |
100 | 6.5 | 228 | |
CDCenDNS | 0 | 100 | 100 |
1 | 85.5 | 115 | |
10 | 43.0 | 132 | |
100 | 25.5 | 179 | |
CDCenPB | 0 | 100 | 100 |
1 | 61.5 | 107 | |
10 | 13.0 | 151 | |
100 | 0.5 | 59.3 | |
AcenNBD | 0 | 100 | 100 |
1 | 103 | 136 | |
10 | 97.5 | 132 | |
100 | 94.5 | 145 | |
AcenDNS | 0 | 100 | 100 |
1 | 96.5 | 139 | |
10 | 97.0 | 136 | |
100 | 87.5 | 151 | |
AcenPB | 0 | 100 | 100 |
1 | 116 | 99 | |
10 | 108 | 95 | |
100 | 102 | 93 |