ABSTRACT
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.
Graphical abstract
Article highlights
This review summarizes the patents consist of the discovery and development of novel URAT1 inhibitors from 2020 to present from the perspective of drug design strategies.
Traditional medicinal chemistry strategies play a crucial role in the structural modification of URAT1 inhibitors.
Dual XOD and URAT1 inhibitors represent a prospective approach to treat hyperuricemia and gout.
Computer-aided drug design is increasingly used for the discovery and optimization of URAT1 inhibitors.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contribution statement
Conception and design of study: Peng Zhan; Acquisition of data: Xiaoyu Shi, Shujing Xu, Jian Zhang; Drafting the manuscript: Xiaoyu Shi, Tong Zhao; Revising the manuscript critically for important intellectual content: Edeildo Ferreira da Silva-Júnior, Shenghua Gao, Xinyong Liu, Peng Zhan.
Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.