Hyperuricemia is a common metabolic condition, cause by increased levels of serum urate (SUA). Reduced excretion of uric acid is reported as the key factor of primary hyperuricemia, accounting for approximately 90% of the cases. Urate transporter 1 (URAT1) is a major protein involved in uric acid reabsorption (about 90%). Therefore, URAT1 inhibitors are considered to be a highly effective and promising class of uricosuric agents for treating hyperuricemia. This review summarizes the development of URAT1 inhibitors for the treatment of hyperuricemia, including approved URAT1 inhibitors, URAT1 inhibitors under development in clinical trials, substances with URAT1 inhibitory effects from derivatives and natural products, and conventional drugs with new uses. This review provides new ideas regarding research on URAT1 inhibitors by introducing the structure, properties, and side effects of chemical drugs, as well as the sources and categories of natural drugs. We also discuss new mechanisms of classic drugs, which may provide guidance to many practicing clinicians. The research and discovery of new inhibitors remain in full swing, and tremendous developments are expected in the field.
Copyright © 2021. Published by Elsevier B.V.