Fig. 2.

Inhibitory potency of non-cholestatic (n = 40) and cholestatic drugs (n = 48) on MRP3-(A) and MRP4-(B) mediated transport. Compounds were classified based on cholestatic potential and further classified as BSEP non-inhibitors versus BSEP inhibitors using an IC₅₀ cutoff of 135 µM based on taurocholate transport in BSEP membrane vesicles. The Left panel indicates ATP-dependent E₂17G (MRP3) (A) and DHEAS (MRP4) (B) uptake measured in the presence of 100 µM compound or vehicle. Data are presented as percent inhibition compared with vehicle-treated control; values show mean ± S.D. of three independent experiments. Compounds are ordered by the magnitude of percent inhibition, and the order does not necessarily match for MRP3 and MRP4 inhibition. Pioglitazone, a cholestatic BSEP inhibitor, was omitted from the MRP3 figure for presentation purposes (mean percent inhibition −166% ± 66%). Right panel indicates box-and-whisker plots of percent MRP3 and MRP4 inhibition by type of liver injury for BSEP non-inhibitors and BSEP inhibitors. The boxes show median (−), mean (+), and upper and lower quartiles. The whiskers indicate the trimmed range of values defined by 1.5 times the interquartile range, whereas values outside the trimmed range are highlighted (●).