Inhibition of cynomolgus monkey and human organic cation transporters by six selected inhibitors
| Compound | IC50 | |||||
|---|---|---|---|---|---|---|
| cOCT2 | hOCT2 | cMATE1 | hMATE1 | cMATE2K | hMATE2K | |
| µM | ||||||
| PYR | 1.2 ± 0.38 | 4.1 ± 0.58 | 0.17 ± 0.04 | 0.11 ± 0.04 | 0.25 ± 0.04 | 0.15 ± 0.01 |
| CMD | 167 ± 15.1 | 200 ± 55.1 | 4.9 ± 1.0 | 2.3 ± 0.29 | 32.2 ± 4.2 | 13.5 ± 4.1 |
| QD | 19.4 ± 2.1 | 19.5 ± 2.1 | 22.0 ± 0.69 | 9.9 ± 1.2 | 18.5 ± 2.7 | 5.2 ± 1.1 |
| VDN | 3.3 ± 0.79 | 7.7 ± 1.0 | 1.4 ± 0.15 | 0.46 ± 0.12 | 0.45 ± 0.04 | 0.30 ± 0.02 |
| KCZ | 0.92 ± 0.17 | 1.6 ± 0.23 | 2.7 ± 0.41 | 1.1 ± 0.13 | 25.0 ± 3.6 | 23.5 ± 2.9 |
| IPM | 12.3 ± 1.8 | 2.1 ± 0.10 | 48.4 ± 5.8 | 37.5 ± 7.2 | 73.5 ± 11.6 | 76.0 ± 17.7 |
Data are shown as mean ± S.D. (n = 3). The IC50 values were determined as indicated under Materials and Methods. MFM (2 µM) was used as substrate. Therefore, the ratio of MFM concentration to Kt is very low (< 0.01) and the reported IC50 values are considered estimates of Ki (assuming competitive inhibition).