Fig. 4: Inhibition of URAT1 by benzbromarone and dotinurad.

a Dose-dependent inhibition of ¹⁴C-urate uptake by benzbromarone (blue) and dotinurad (red) on wild-type URAT1. Data are shown as “mean values ± SEM” Three independent replicates were performed, and all curves were fitted by nonlinear regression. b Schematic representation of the interaction networks between benzbromarone and dotinurad with URAT1 residues, depicted in 2D format, including the division of ligand regions. c The interaction network between benzbromarone and URAT1 residues is depicted. Hydrogen bonds are highlighted with red dashed lines, and the corresponding density maps of the residues and ligand are shown as a mesh (contour level: σ = 5). d The interaction network between dotinurad and URAT1 residues is depicted. Hydrogen bonds are highlighted with red dashed lines, and the corresponding density maps of the residues and ligands are shown as a mesh (contour level: σ = 7). e, f Dose-dependent inhibition of ¹⁴C-urate uptake by benzbromarone (e) and dotinurad (f) in wild-type URAT1 and URAT1 mutants. g Structural alignment of benzbromarone and dotinurad in URAT1.