Fig. 7.

Pairwise comparisons of IC₅₀ values (micromolar) for the inhibition of OCT2-mediated transport of structurally distinct substrates. (A) Pairwise comparison of IC₅₀ values for the inhibition of OCT2-mediated transport of metformin (x-axis) and MPP (y-axis) determined for a subset of 20 compounds selected from the NCC (Table 2) (note the pairwise comparison of IC₅₀ values for irinotecan, shown as an open circle). Each IC₅₀ value is the mean ± S.E. (n = 2) of values determined in two separate experiments using the experimental design used for the experiments presented in Fig. 6 (also Supplemental Fig. 2). In this comparison (and the others), the line of unity (equal IC₅₀ values for the inhibition of both substrates) is represented by the solid red line, and dashed lines represent ratios of IC₅₀ values that differ from one another by 3-fold. Pairwise comparison of measured (x-axes) and predicted IC₅₀ values for the inhibition of MPP transport (B) or metformin transport (C). Measured values are those shown in (A) (Table 2); predicted values were calculated using the single-point method (see Materials and Methods). (D) Pairwise comparisons of predicted IC₅₀ values for the inhibition of metformin transport against those for MPP transport for 162 compounds from the NCC that inhibited transport by between 10% and 90%.