Inhibitor | Category | Substrate | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[14C]metformin | [3H]thiamine | [3H]MPP+ | [3H]E3S | Rhodamine 123 | ||||||||||||
IC50 (μM), MATE1 | ||||||||||||||||
Pyrimethamine | Drug with known DDI | 0.313 | ± | 0.052 | 0.330 | ± | 0.052 | 0.492 | ± | 0.039 | 0.150 | ± | 0.057 | 1.16 | ± | 0.13 |
Cimetidine | Drug with known DDI | 2.56 | ± | 0.04 | 3.19 | ± | 0.04 | 4.43 | ± | 0.05 | 1.30 | ± | 0.06 | 36.8 | ± | 0.2 |
Trimethoprim | Drug with known DDI | 4.13 | ± | 0.09 | 4.19 | ± | 0.05 | 8.16 | ± | 0.06 | 2.69 | ± | 0.03 | >100 | ||
Zosuquidar | P-gp inhibitor | >50 | >50 | >50 | >50 | >50 | ||||||||||
Valspodar | P-gp inhibitor | 2.67 | ± | 0.05 | 4.83 | ± | 0.06 | 5.89 | ± | 0.05 | 2.02 | ± | 0.07 | >15 | ||
Quinidine | P-gp inhibitor | 5.82 | ± | 0.06 | 6.77 | ± | 0.05 | 6.77 | ± | 0.08 | 6.96 | ± | 0.06 | >100 | ||
Ondansetron | High inhibition potency | 0.436 | ± | 0.083 | 0.493 | ± | 0.041 | 0.797 | ± | 0.025 | 0.287 | ± | 0.029 | 3.96 | ± | 0.07 |
Famotidine | Selectivity (MATE1 > MATE2-K) | 0.905 | ± | 0.046 | 1.20 | ± | 0.03 | 1.67 | ± | 0.03 | 0.456 | ± | 0.036 | 6.72 | ± | 0.16 |
Topotecan | Selectivity (MATE1 > MATE2-K) | 5.34 | ± | 0.03 | 4.49 | ± | 0.03 | 8.25 | ± | 0.05 | 2.66 | ± | 0.03 | 26.9 | ± | 0.1 |
NBuPy-Cl | Selectivity (MATE2-K > MATE1) | 55.2 | ± | 0.1 | 83.5 | ± | 0.1 | 76.8 | ± | 0.1 | 51.8 | ± | 0.1 | >100 | ||
IC50 (μM), MATE2-K | ||||||||||||||||
Pyrimethamine | Drug with known DDI | 0.180 | ± | 0.083 | 0.372 | ± | 0.068 | 0.650 | ± | 0.063 | 0.372 | ± | 0.112 | 0.833 | ± | 0.130 |
Cimetidine | Drug with known DDI | 5.47 | ± | 0.06 | 11.2 | ± | 0.0 | 13.4 | ± | 0.1 | 11.2 | ± | 0.1 | 30.5 | ± | 0.1 |
Trimethoprim | Drug with known DDI | 0.421 | ± | 0.052 | 0.440 | ± | 0.027 | 1.22 | ± | 0.03 | 0.440 | ± | 0.047 | 1.05 | ± | 0.12 |
Zosuquidar | P-gp inhibitor | >50 | >50 | >50 | >50 | >50 | ||||||||||
Valspodar | P-gp inhibitor | 0.118 | ± | 0.039 | 0.169 | ± | 0.025 | 0.238 | ± | 0.034 | 0.109 | ± | 0.031 | 0.219 | ± | 0.050 |
Quinidine | P-gp inhibitor | 6.44 | ± | 0.06 | 11.7 | ± | 0.1 | 17.6 | ± | 0.1 | 14.7 | ± | 0.2 | 28.5 | ± | 0.1 |
Ondansetron | High inhibition potency | 0.259 | ± | 0.086 | 0.597 | ± | 0.071 | 0.725 | ± | 0.055 | 0.430 | ± | 0.086 | 1.74 | ± | 0.07 |
Famotidine | Selectivity (MATE1 > MATE2-K) | 3.10 | ± | 0.09 | 5.30 | ± | 0.07 | 8.88 | ± | 0.05 | 6.66 | ± | 0.10 | 24.1 | ± | 0.1 |
Topotecan | Selectivity (MATE1 > MATE2-K) | 5.43 | ± | 0.04 | 9.15 | ± | 0.04 | 15.8 | ± | 0.0 | 6.11 | ± | 0.08 | 14.7 | ± | 0.1 |
NBuPy-Cl | Selectivity (MATE2-K > MATE1) | >100 | >100 | 86.5 | ± | 0.1 | >100 | >100 |
DDI, drug-drug interaction; P-gp, P-glycoprotein.