URAT1 inhibitor 3 is a potent, orally active, selective inhibitor of URAT1 (IC50 = 0.8 nM) demonstrating urate-lowering efficacy, suitable for research in gout and hyperuricemia [1].

URAT1 inhibitor 3, at concentrations ranging from 0-400 μM, demonstrated low toxicity and inhibited the viability of HepG2 and HK2 cells only at higher concentrations, over periods of 24 and 72 hours, with minimal cytotoxic effects noted at the 24-hour mark and an inhibition rate of 34.75% for HepG2 cells and 35.9% for HK2 cells. Additionally, at doses between 0.01-100 μM, this inhibitor displayed reduced effectiveness against urate excretion transporters, possessing IC 50 values of 10.16 μM for OAT1 and 4.04 μM for ABCG2, indicating a lesser impact on these specific transporters compared to its overall cell viability effects.

URAT1 inhibitor 3, administered via oral gavage to male Kunming mice in a hyperuricemia model, demonstrated urate-lowering efficacy at doses of 1-4 mg/kg in a single dose, significantly reducing serum urate levels in a dose-dependent manner without causing hepatic or renal toxicities when administered daily at 50 mg/kg over 14 days. Additionally, a single dose of 50 mg/kg resulted in a notable depletion of serum GSH levels from 42.23 μM to 20.39 μM, indicating its impact on oxidative stress markers in this model [1].