Novel urate transporter 1 (URAT1) inhibitors: a review of recent patent literature (2020–present)

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

KEYWORDS:

• Drug design
• gout
• hyperuricemia
• medicinal chemistry
• URAT1 inhibitors

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.

Additional information

Funding

This paper was funded by the Shandong Provincial Key research and development project (2019JZZY021011), Science Foundation of Outstanding Young Scholars of Shandong Province (ZR2020JQ31), Qilu Young Scholars Program of Shandong University, and the Taishan Scholar Program at Shandong Province.