Introduction: The urate transporter 1 (URAT1) is a membrane transporter located in the apical membrane of human renal proximal tubule epithelial cells, which mediates most of the reabsorption of urate. Hyperuricemia (HUA) is a common disease caused by metabolic disorders, which has been considered as the key factor of gout. Approximately 90% of patients suffer from hyperuricemia due to insufficient or poor uric acid excretion. Therefore, the drug design of URAT1 inhibitors targeting improve the renal urate excretion by reducing the reabsorption of urate anions represent a hot topic in searching for anti-gout drugs currently.
Areas covered: In this review, we summarize URAT1 inhibitors patents reported since 2020 to present through the public database at https://worldwide.espacenet.com and some medicinal chemistry strategies employed to develop novel drug candidates.
Expert opinion: Ligand-based drug design (LBDD) strategies have been frequently used developing new URAT1 inhibitors. Meanwhile, the discovery of dual drugs targeting both inhibition of xanthine oxidase (XOD) and URAT1 may be an emerging horizon for designing novel uric acid-lowering candidates in future. Furthermore, advanced techniques in the field of molecular biology and computer science can increase the chances to discover and/or optimize URAT1 inhibitors, contributing to the development of novel drug candidates.
Keywords: Drug design; URAT1 inhibitors; gout; hyperuricemia; medicinal chemistry.