Recent Updates of Natural and Synthetic URAT1 Inhibitors and Novel Screening Methods

Abstract

Human urate anion transporter 1 (hURAT1) is responsible for the reabsorption of uric acid in the proximal renal tubules and is a promising therapeutic target for treating hyperuricemia. To mitigate the side effects of URAT1-targeted clinical agents such as benzbromarone, there is significant interest in discovering new URAT1 inhibitors and developing technology that can evaluate URAT1 inhibition. This review summarizes the methods for assay of URAT1 inhibition and the progress on the discovery of natural and synthetic URAT1 inhibitors in the past five years.

A Brief Review of Natural Products with Urate Transporter 1 Inhibition for the Treatment of Hyperuricemia

“…Reducing purine intake, inhibiting uric acid production, and promoting uric acid excretion are e ective ways to treat or improve hyperuricemia [9]. URAT1 inhibitors are a widely used class of uricosuric drugs by inhibiting the reabsorption of uric acid, such as probenecid, sul npyrazone, and benzbromarone [10]. Although these drugs have good uric acid lowering e ects, they all have varying degrees of side e ects [11].…”

Effect of Food on the Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of SHR4640, a Selective Urate Transporter 1 Inhibitor, in Healthy Chinese Male Volunteers

“…The URAT1 inhibitors are developed as a promising therapeutic target for hyperuricemia and gout therapies. [7][8][9] Currently, URAT1 inhibitors including probenecid, benzbromarone, sulfinpyrazone, and lesinurad were approved in the market. 8 SHR4640, also identified as ruzinurad, a highly selective URAT1 inhibitor, was developed for the treatment of hyperuricemia and gout.…”

“…[7][8][9] Currently, URAT1 inhibitors including probenecid, benzbromarone, sulfinpyrazone, and lesinurad were approved in the market. 8 SHR4640, also identified as ruzinurad, a highly selective URAT1 inhibitor, was developed for the treatment of hyperuricemia and gout. The compound ruzinurad is formulated as 1-[(6-bromoquinolin-4-yl) sulfanyl] cyclobutane-1-carboxylic acid, 9 and SHR4640 is the sodium salt of ruzinurad.…”

“…Human urate transporter 1 (URAT1), as a transporter responsible for uric acid reabsorption, plays an important role in regulation of sUA levels. The URAT1 inhibitors are developed as a promising therapeutic target for hyperuricemia and gout therapies 7–9 . Currently, URAT1 inhibitors including probenecid, benzbromarone, sulfinpyrazone, and lesinurad were approved in the market 8 …”

“…The URAT1 inhibitors are developed as a promising therapeutic target for hyperuricemia and gout therapies 7–9 . Currently, URAT1 inhibitors including probenecid, benzbromarone, sulfinpyrazone, and lesinurad were approved in the market 8 …”