Cell experiment:

Validated oocytes, HEK293, MDCK-II, Caco-2 or MDCK-MDR1 cell systems are used to study the interaction of Lesinurad with membrane transporters localized to the kidney (OAT1, OAT3, OCT2, MATE1, and MATE2K) or liver (P-gp, BCRP, OATP1B1, OATP1B3, and OCT1). Xenopus laevis oocytes are injected with OAT1 or OAT3 cRNA or control (water) while HEK293 cells are stably transfected with MATE1, MATE2K, or vector and MDCK-II cells with hOATP1B1, hOATP1B3, hOCT1, hOCT2, or vector. The MDCKII cell line is stably transfected with the human MDR1 gene to create a P-gp cell line. The interaction of Lesinurad with BCRP relied on the endogenous expression in Caco-2 cells. All cells are cultured with growth medium according to standard methodology. In order to determine whether Lesinurad is a substrate for a transporter, cells are incubated with [14C]-labeled Lesinurad at various concentrations and the amount of Lesinurad taken up by the cells determined by subtracting the uptake in vector cells from that in the transfected cells. The uptake of a [3H]-labeled known substrate of the transporter served as the positive control. Inhibition of a transporter by Lesinurad is determined by incubating cells with a fixed concentration of [3H]-labeled known substrate and various concentrations of unlabeled Lesinurad. Inhibition by a known inhibitor of each transporter served as the positive control. Cells are incubated for the appropriate amount of time. All reactions are terminated by the addition of ice-cold medium. The cells are then rinsed with medium and lysed[1].

Lesinurad is an inhibitor of URAT1 that promoting renal uric acid excretion [1].URAT1 is a transporter in the kidney that regulates uric acid excretion from the body [2].
In the clinical study, lesinurad potently inhibit URAT1 as well as OAT4, another transporter responsible for the renal resorption of urate. In a study, 21 people with hyperuricemia or gout (sUA >= 8.0 mg/dL) were randomized to lesinurad, open-label allopurinol or placebo. Most of the lesinurad-treated patients had sUA < 6 mg/dL after seven days, which were the same effect to patients receiving allopurinol and better than placebo. Also, Lesinurad showed well tolerated in the study [2]. Compared with probenecid, whose efficacy is reducing patients with renal insufficiency, lesinurad may be effective in patients with mildly impaired renal function [1].
References:
[1]. Crittenden DB, Pillinger MH. New therapies for gout. Annu Rev Med, 2013, 64: 325-337.
[2]. Singh JA. Emerging therapies for gout. Expert Opin Emerg Drugs, 2012, 17(4): 511-518.