Inhibitors | OCT2 IC50 or Ki (µM) | MATE1 IC50 or Ki (µM) | MATE2K IC50 or Ki (µM) | OAT2 IC50 or Ki (µM) | OCT3 IC50 or Ki (µM) | |||
---|---|---|---|---|---|---|---|---|
Probe Metformin (10 µM)a | Reported in the Literatureb | Probe Metformin (5 µM)a | Reported in the Literatureb | Probe Metformin (5 µM)a | Reported in the Literatureb | Reported in the Literatureb | Reported in the Literatureb | |
Cimetidine | 2.9 ± 0.7 | 16.6–1650 | 0.6 ± 0.05 | 0.2–16.3 | 5.6 ± 0.7 | 2.1–46.6 | 22–72.8 | 9.8–111 |
Pyrimethamine | 0.61 ± 0.04 | 4.8–23.6 | 0.02 ± 0.002 | 0.077–0.63 | 0.045 ± 0.003 | 0.046–0.52 | — | — |
Famotidine | 21.6 ± 3.4 | 36.1–1800 | 0.45 ± 0.03 | 0.6–0.76 | 6.6 ± 0.9 | 9.7–36.2 | — | 6.7–14 |
Ranitidine | 11.7 ± 1.3 | 30.5–79 | 8.2 ± 0.6 | 8.3–25.4 | 21 ± 2 | 25 | — | 62–290 |
Trimethoprim | 19.8 ± 1.5 | 13.2–1327 | 0.51 ± 0.03 | 3.31–29.1 | 0.14 ± 0.02 | 0.61–28.9 | NI | 12.3 |
Dronedarone | 1.9 ± 0.3 | — | 0.46 ± 0.02 | — | 8.9 ± 1.7 | — | — | — |
DX-619 | — | 0.94–1.29 | — | 0.82–4.32 | — | 0.1 | — | — |
Dolutegravir | 0.21 ± 0.04 | 0.066–1.93 | 3.6 ± 0.7 | 4.67 | 12.5 ± 1.6 | >100 | >100 | >100 |
Cobicistat | 37.9 ± 4.9 | 8.24–33 | 0.98 ± 0.19 | 0.99–1.87 | 20.5 ± 3.0 | 33.5 | >100 | >100 |
Ritonavir | 24.8 ± 3.4 | 20–25 | 0.28 ± 0.05 | 0.08–15.4 | 40.1 ± 6.5 | 23.7 | >20 | 300 |
Ranolazine | 47 ± 9 | — | 16.8 ± 1.5 | — | 50 ± 8 | — | — | — |
Rilpivirine | 0.38 ± 0.05 | 5.13 | 0.25 ± 0.04 | — | 0.28 ± 0.08 | — | — | — |
Amiodarone | 4.7 ± 1.1 | >1000 | 1.0 ± 0.2 | — | >50 | — | — | >1000 |
Raltegravir | >100 | >100 | >100 | >100 | >100 | >100 | — | — |
Telaprevir | >100 | 6.35 | 62 ± 5 | 22.98 | >100 | — | — | — |
Vandetanib | 0.4 ± 0.05 | 5.5–73.4 | 0.06 ± 0.01 | 0.16–1.23 | 0. 04 ± 0.01 | 0.3–1.26 | — | — |
—, Data are not reported or available; NI, no inhibition.
↵a Data generated at Merck & Co. for inhibition of OCT2, MATE1, and MATE2K using metformin as the probe substrate in CHO-K1-OCT2, CHO-K1-MATE1, and MDCKII-MATE2K cells using the method described by Rizk et al. (2014).
↵b Data obtained from the University of Washington DDI database (https://www.druginteractioninfo.org).