Inhibition of substrate uptake into transporter-transfected HEK293 cells
| IC50a | ||||||||
|---|---|---|---|---|---|---|---|---|
| Inhibitor | OAT1 | OAT3 | OCT2 | MATE1 | MATE2K | |||
| PAHb | E3S | MPP+ | Metformin | MPP+ | Metformin | MPP+ | Metformin | |
| µM | µM | µM | µM | µM | µM | µM | µM | |
| Vandetanib | >100 | >100 | 73.4 ± 14.8 | 8.8 ± 1.9c | 1.23 ± 0.05d | 0.16 ± 0.05ce | 1.26 ± 0.06d | 0.30 ± 0.09ce |
| (60)f | (55) | (58) | (29) | |||||
| Probenecid | 27.4 ± 5.6 | 18.7 ± 5.3 | ND | ND | ND | ND | ND | ND |
| PYR | ND | ND | 23.6 ± 3.7 | 4.8 ± 1.0c | 0.63 ± 0.07d | 0.11 ± 0.02ce | 0.52 ± 0.17d | 0.10 ± 0.02ce |
| (37)f | (44) | (45) | (48) | |||||
ND, not determined.
↵a IC50 value obtained at a final substrate concentration of 1 µM (see Materials and Methods). Data are reported as the mean ± S.D. (n = 3 determinations).
↵b Substrate used to generate IC50.
↵c Statistically significant difference compared with IC50 of MPP+ uptake in same cell line (P < 0.0001).
↵d Statistically significant difference compared with IC50 of MPP+ uptake in OCT2-HEK cells (P < 0.0001).
↵e Statistically significant difference compared with IC50 of metformin uptake in OCT2-HEK cells (P < 0.0001).
↵f Number in parentheses represents the IC50 ratio (OCT2 versus MATE1 or MATE2K).