TABLE 5

BCRP IC50 (in micromolar concentrations) measured in membrane vesicles using either E3S (1 µM) or MTX (2 µM) as model substrates and measured in M-BCRP cells using PhIP (2 µM) as model substrate

Compound NameSubstrate (System): 3H-E3S (Vesicles)Substrate (System): 3H-MTX (Vesicles)Substrate (System): 14C-PhIP (M-BCRP)E3S/MTX IC50 Fold Substrate DependencyM-BCRP/Vesicles IC50 Fold System Dependency
Ko1430.015 ± 0.0050.052 ± 0.0010.020 ± 0.0010.30.4
Elacridar0.15 ± 0.040.60 ± 0.130.16 ± 0.070.30.3
Imatinib0.16 ± 0.020.34 ± 0.050.46 ± 0.040.51.4
FTC0.25 ± 0.020.45 ± 0.080.20 ± 0.010.60.4
Topotecan HCl0.67 ± 0.211.32 ± 0.25>1500.5114
MK5711.66 ± 0.450.078 ± 0.02537.3 ± 6.021478
Eltrombopag3.4 ± 0.13.1 ± 1.335.7 ± 3.31.112
Rapamycin (sirolimus)4.7 ± 0.55.3 ± 0.71.5 ± 0.30.90.3
Ritonavir7.2 ± 1.68.6 ± 2.019.5 ± 1.80.82.3
Pantoprazole11.2 ± 1.49.7 ± 2.216.5 ± 1.41.11.7
Zosuquidar12.5 ± 2.314.4 ± 2.771 ± 190.94.9
Omeprazole13.4 ± 1.816.8 ± 10.425.7 ± 2.80.81.5
CsA15.8 ± 3.14.6 ± 0.711.1 ± 2.73.42.4
E3SNA17.7 ± 1.5> 300NA17
Verapamil80.8 ± 8.983.7 ± 23.7149 ± 251.01.8
MTX>100NA>500NANA
Vincristine>150>150>150NANA
Fexofenadine>300>300>300NANA
Metformin>300>300>300NANA
  • NA, not applicable; >, when no inhibition was observed, the IC50 was considered higher than the highest soluble concentration in buffer (in micromolar concentrations).