Fig. 1: SR-THAP is a selective non-competitive inhibitor of hGAT3.
From: Structural basis for selective inhibition of human GABA transporter GAT3
a SR-THAP inhibits [3H]GABA uptake by hGAT3 expressed in HEK293T cells with an IC50 of 25.2 [21.8; 30.4] μM without preincubation (blue) and 4.4 [3.6; 5.2] µM, 4.5 [3.4; 5.9] µM, and 4.9 [3.3; 7.0] μM after 15, 30, and 120 min preincubation, respectively. b The enantiomer RS-THAP inhibits [3H]GABA uptake by hGAT3 expressed in HEK293T cells, but with significantly reduced potency, with estimated IC50 values of >600 μM without preincubation and >100 μM with preincubation. c [3H]GABA uptake by hGAT3 can also be inhibited by non-radioactive GABA, although showing minimal shift in potency after 120 min preincubation, with IC50 values of 8.5 [6.4; 11] and 5.4 [4.6; 6.4] μM, respectively. d [3H]GABA uptake kinetic experiment fitted to the Michaelis–Menten model, performed with increasing concentrations of SR-THAP without preincubation (left) or after 120 min of preincubation (middle), before addition of [3H]GABA. Right panel shows the Michaelis–Menten kinetic parameters derived from the graphs in the left and middle panels, without (top) and with (bottom) 120 min preincubation. Statistical differences from control were determined by a two-sided F test and are indicated with stars as: * - P ≤ 0.05, ** - P ≤ 0.01. For reference, the F-test p values were 0.029 (0.5 µM), 0.0021 (2 µM), and 0.0015 (10 µM) without preincubation, and 0.652 (0.5 µM) and 0.0022 (2 µM) with preincubation. Data points are shown as individual replicates from n = 3 biological replicates (triplicate measurements) unless otherwise stated. Source data are provided as a Source data file.
