Figure 1

(A) Lesinurad (1) structurally resembles the dual PPARα/PPARγ agonist WY14,643 (2) and shares the typical architecture of fatty acid mimetics. (B) Molecular docking of lesinurad (1) into the PPARγ ligand binding domain (PDB-ID: 3ET317) suggests a very favorable binding mode. The carboxylic acid of 1 forms neutralizing contacts with the triad of Ser289, His323, His449 and Tyr473 and the triazole moiety participates in π-interactions with Cys285 and His449. Lesinurad’s hydrophobic tail is placed in a lipophilic arm of the PPARγ ligand binding site.