Figure 4

Isothermal titration calorimetry (ITC, recombinant PPARγ ligand binding domain was titrated to lesinurad due to the drug’s limited aqueous solubility) confirmed direct interaction of lesinurad with the PPARγ ligand binding domain and revealed an independent Kd value of 1.3 μM. Binding was driven by enthalpic (ΔH = −26 kJ/mol) and entropic (ΔS = 27 J/mol·K) shares confirming the proposed binding mode which revealed two H-bonds and several lipophilic contacts.