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

Ying Chen,Yousheng Wang,Ruya You,Ke Wang,Sandrina A Heleno

doi:10.1155/2021/5738900

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.

Highlights

Uric acid is the final product of purine metabolism in the human body [1, 2]
E oral administration of orange juice (5 mL/kg) and hesperetin (5 mg/kg) significantly reduced the serum uric acid in potassium oxonate (PO-)induced hyperuricemia rats by 38.76% and 24.93%, respectively, while allopurinol significantly decreased by 124%. e dominant flavonoids in orange juice are hesperidin and narirutin, which are hydrolyzed to hesperetin and naringenin in the colon [38]
HURAT1-cRNA must be synthesized, injected into the cells, and incubated for 2-3 days. e oocytes are transferred to a Cl−-free solution containing [14C] uric acid to initiate the uptake of uric acid, while the radioactivity in the oocytes is determined by a liquid scintillation counter [71], considering that the oocyte cell model is complicated and the renal localization of URAT1, kidney cell HEK293, or MDCK cells have been used in recent years to express Human urate anion transporter 1 (hURAT1) [67, 68]

Summary

Introduction

Uric acid is the final product of purine metabolism in the human body [1, 2]. More people suffer from an unbalanced urate metabolism [3]. Ere are currently three treatments for hyperuricemia: reduction of urate production, increase in urate excretion, and decomposition of urate. Statistics indicate that 90% of hyperuricemia cases are due to impaired renal uric acid excretion and that only 10% are due to excessive production of uric acid [16]. E kidneys and intestines play a major role in uric acid excretion, with more than 70% of urate excretion taking place in the renal pathway. The development of reagents for increasing uric acid excretion has significant therapeutic potential

Methods

Results

Conclusion