TABLE 4

IC50 values for multidrug and toxin extrusion (MATE)1- and MATE2-K-mediated uptake of [14C]metformin, [3H]thiamine, [3H]MPP+, [3H]E3S, and rhodamine 123

Uptake of [14C]metformin (10 μM, 1 min), [3H]thiamine (1 μM, 1 min), [3H]MPP+ (1 μM, 1 min), [3H]E3S (10 μM, 2 min), and rhodamine 123 (1 μM, 2 min) was determined in the absence and presence of various concentrations of inhibitors. IC50 values were estimated by nonlinear regression analysis and are given as mean ± S.D. from one experiment.

InhibitorCategorySubstrate
[14C]metformin[3H]thiamine[3H]MPP+[3H]E3SRhodamine 123
IC50 (μM), MATE1
PyrimethamineDrug with known DDI0.313±0.0520.330±0.0520.492±0.0390.150±0.0571.16±0.13
CimetidineDrug with known DDI2.56±0.043.19±0.044.43±0.051.30±0.0636.8±0.2
TrimethoprimDrug with known DDI4.13±0.094.19±0.058.16±0.062.69±0.03>100
ZosuquidarP-gp inhibitor>50>50>50>50>50
ValspodarP-gp inhibitor2.67±0.054.83±0.065.89±0.052.02±0.07>15
QuinidineP-gp inhibitor5.82±0.066.77±0.056.77±0.086.96±0.06>100
OndansetronHigh inhibition potency0.436±0.0830.493±0.0410.797±0.0250.287±0.0293.96±0.07
FamotidineSelectivity (MATE1 > MATE2-K)0.905±0.0461.20±0.031.67±0.030.456±0.0366.72±0.16
TopotecanSelectivity (MATE1 > MATE2-K)5.34±0.034.49±0.038.25±0.052.66±0.0326.9±0.1
NBuPy-ClSelectivity (MATE2-K > MATE1)55.2±0.183.5±0.176.8±0.151.8±0.1>100
IC50 (μM), MATE2-K
PyrimethamineDrug with known DDI0.180±0.0830.372±0.0680.650±0.0630.372±0.1120.833±0.130
CimetidineDrug with known DDI5.47±0.0611.2±0.013.4±0.111.2±0.130.5±0.1
TrimethoprimDrug with known DDI0.421±0.0520.440±0.0271.22±0.030.440±0.0471.05±0.12
ZosuquidarP-gp inhibitor>50>50>50>50>50
ValspodarP-gp inhibitor0.118±0.0390.169±0.0250.238±0.0340.109±0.0310.219±0.050
QuinidineP-gp inhibitor6.44±0.0611.7±0.117.6±0.114.7±0.228.5±0.1
OndansetronHigh inhibition potency0.259±0.0860.597±0.0710.725±0.0550.430±0.0861.74±0.07
FamotidineSelectivity (MATE1 > MATE2-K)3.10±0.095.30±0.078.88±0.056.66±0.1024.1±0.1
TopotecanSelectivity (MATE1 > MATE2-K)5.43±0.049.15±0.0415.8±0.06.11±0.0814.7±0.1
NBuPy-ClSelectivity (MATE2-K > MATE1)>100>10086.5±0.1>100>100
  • DDI, drug-drug interaction; P-gp, P-glycoprotein.