Kinetic parameters of each compound on OAT1
| Compound | IC50 (μM)a | Km of Efflux (μM)a | Estimated pKa of Hydroxyl Groupb |
|---|---|---|---|
| FAMTc | 453.1 ± 14.3d | 690.8 ± 18.9d | 8.4 |
| IMT | 118.5 ± 12.7 | 146.8 ± 11.3 | 8.4 |
| 4-I-m-Tyr | 737.5 ± 12.1 | 452.7 ± 10.1 | 8.3 |
| 3-IT | 236.2 ± 12.7 | 73.8 ± 6.8 | 8.3 |
| 3-FT | 757.1 ± 16.4 | 339.4 ± 13.4 | 8.4 |
| 3-I-AMP | N.D.e | ||
| 3-F-AMP | N.D. | ||
| AMT | N.D. | 9.3 | |
| 2-FAMT | N.D. | 8.5 | |
| 2-IT | 82.3 ± 15.6 | 64.0 ± 6.4 | 8.8 |
| 2-FT | N.D. | 1166 ± 18.3 | 8.8 |
| 2-F-m-Tyr | 749.4 ± 24.6 | 8.3 | |
| 4-F-m-Tyr | 534.6 ± 10.3 | 419.4 ± 19.7 | 8.3 |
| 5-F-m-Tyr | 371.5 ± 7.2 | 8.4 | |
| 6-F-m-Tyr | N.D. | 8.9 | |
| 3-F-o-Tyr | 401.3 ± 9.1 | 8.2 | |
| 4-F-o-Tyr | 607.8 ± 11.4 | 8.3 | |
| 5-F-o-Tyr | 852.5 ± 13.4 | 8.7 | |
| 6-F-o-Tyr | 756.5 ± 19.6 | 8.3 |
↵a IC50 of the compound to inhibit OAT1-mediated [14C]PAH (1 μM) uptake and the Km to induce OAT1-mediated [14C]PAH efflux were determined in OAT1 cells as described in Materials and Methods.
↵b The pKa value of hydroxyl group on the benzene ring was estimated by the Calculator Plugins, MarvinSketch version 20.14.0 (ChemAxon).
↵c Kinetic parameters of OAT1-mediated [14C]FAMT uptake were further determined: Km, 171.9 ± 16.6 μM; Vmax, 3391 ± 27.3 pmol/mg per minute.
↵d Values represent mean ± S.D. (n = 4).
↵e N.D. indicates “not determined.”