Structural determinants of inhibitor interaction with the human organic cation transporter OCT2 (SLC22A2)

The organic cation transporter 2 (OCT2) provides an important pathway for the uptake of cationic compounds in the kidney, which is the essential step in their elimination from the organism. Although many drugs have been identified which interact with human OCT2, structural elements required for an interaction with OCT2 are not well defined. To address this issue, HEK293 cells stably expressing human OCT2 were generated. IC 50 values of commonly used drugs for inhibition of [ 3 H]MPP + uptake were determined and correlated with physicochemical descriptors. We found only a significant correlation between the topological polar surface area (TPSA) and IC 50 values ( r = 0.71, p