URAT1 (urate transporter 1), a member of the OAT (organic anion transporter) family, where is localized to the apical (brush border) membrane of renal proximal tubular cells. Moreover, URAT1 mediates the reabsorption of uric acid, thereby regulating blood uric acid concentrations. In the kidney, URAT1 exists in the renal tubular cell membrane and is involved with the reabsorption and excretion of uric acid, organic acids, drugs and their metabolites.
In addition to URAT1, OAT1 and OAT3 are also SLC22A family members and transport urate in the kidney. OAT1 and OAT3 can take up uric acid from the blood and reabsorbed into renal tubular cells via URAT1, in exchange for dicarboxylic acid. Furthermore, URAT1 functions to transport organic and uric acids throughout the salivary glands. Here, we will introduce an URAT1 inhibitor, Epaminurad.
Epaminurad (UR-1102) is an orally active, potent and selective URAT1 inhibitor.
Epaminurad shows high selectivity to URAT1 over OAT1 and OAT3 in vitro. For example, in HEK293 cells overexpressing URAT1, OAT1, and OAT3, Epaminurad effectively inhibits URAT1, whereas it quite modestly inhibits OAT1 and OAT3. Moreover, Epaminurad is also a uricosuric agent. For instance, in tufted capuchin monkeys, Epaminurad (0-30 mg/kg; oral administration; for 3 days) shows uricosuric and urate-lowering effects. In addition, Epaminurad has a good pharmacokinetic profile, and effectively reduces plasma uric acid. More importantly, Epaminurad does not cause liver toxicity in animals. These results show that Epaminurad achieves potent uric acid excretion through selective inhibition of URAT1 in monkeys. Epaminurad has the potential for the research of gout and hyperuricemia.
To sum up, Epaminurad is an orally active, potent and selective URAT1 inhibitor. And it has the potential for the research of gout and hyperuricemia.