Fig. 2: Structural basis of LAT1 inhibition by JPH203.

a, b Close-up views of the JPH203-binding site. Interacting residues are shown as stick models. Hydrogen bonds are depicted as dotted lines. The 5-amino group of JPH203 is marked by an asterisk. The previously predicted “distal pocket” is marked by gray dotted circles. c Schematic diagram of the interactions between JPH203 and LAT1. Hydrogen bonds are depicted as black dashed lines. Hydrophobic contacts are depicted by green splines. A π–π interaction is depicted as a green dashed line connecting two green dots. d Inhibition of LAT1 by JPH203 at different concentrations. Uptake of ʟ-[¹⁴C]Leu into Xenopus oocytes expressing co-expressing CD98hc and wild-type or F252W LAT1 was measured in the presence of JPH203 at indicated concentrations. As a negative control, water was injected instead of cRNAs. Data are mean ± SD and each data point represents a single oocyte (n = 7 for 0.03, 0.3, 1 and 10 μM for WT; n = 8 for 0, 0.01 and 3 μM for WT and 3 and 10 μM for F252W; n = 9 for 0.003 and 0.1 for WT and 0, 0.003, 0.03, 0.1 and 1 for F252W; and n = 10 for 0.01 and 0.3 for F252W). e Concentration-dependent inhibition curves by JPH203 for wild-type or F252W LAT1, calculated using the same data as shown in panel (d). Source data are available with this paper as Source Data file.