Table 2.
Reference Inhibitor and Competitive Substrate of ABCG2 Restore Sensitivity of PF-4989216 to ABCG2-Overexpressing Cell Lines
| IC50 (μM)a |
|||
|---|---|---|---|
| cell line | PF-4989216 | PF-4989216 + Ko143 (1 μM) | PF-4989216 + lapatinib (0.3 μM) |
| S1 | 1.11 ± 0.09 | 1.62 ± 0.11 | 0.96 ± 0.11 |
| S1-M1-80 | 6.79 ± 1.00 | 2.36 ± 0.49**b | 1.56 ± 0.25*** |
| H460 | 0.93 ± 0.11 | 1.04 ± 0.18 | 0.86 ± 0.11 |
| H460-MX20 | 4.03 ± 0.51 | 1.12 ± 0.22*** | 1.20 ± 0.16*** |
| pcDNA-HEK293 | 0.44 ± 0.05 | 0.40 ± 0.09 | 0.41 ± 0.07 |
| R482-HEK293 | 5.05 ± 0.89 | 0.82 ± 0.17*** | 2.26 ± 0.50** |
a
IC50 values are mean ± SD of PF-4989216 in the presence and absence of a reference inhibitor of ABCG2. The IC50 values were calculated from dose–response curves obtained from at least three independent experiments.
b*
P < 0.05
**
P < 0.01
***
P < 0.001.