Introduction: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a key target for the treatment of gout and other hyperuricemia-related conditions.
Areas covered: This paper reviews XO inhibitors in patents from 2021 to the present. We summarize in detail the structural classes and characteristics, in vitro and in vivo biological results, and structure‒activity relationships of synthetic inhibitors, as well as the sources, specific structures, research methods, and biological activities of XO inhibitors from natural products.
Expert opinion: (1) Benefiting from the discovery of many high-affinity inhibitors, the binding modes of small molecules in the active pocket of XO have been further elucidated, and this information will contribute to future development; (2) natural products remain one of the important sources in the discovery of XO inhibitors; (3) with a deeper exploration of XO and URAT1 targets, XO/URAT1 dual target inhibitors may be a future research hotspot; and (4) the search for high-affinity, small-molecule scaffolds remains a key challenge and an important direction for the future development.
Keywords: SAR; Xanthine oxidase inhibitors; gout; hyperuricemia; uric acid.