Recent Progress and Future Perspectives on Anti-Hyperuricemic Agents

Increased biosynthesis or underexcretion of uric acid (UA or urate) in the body ultimately leads to the development of hyperuricemia. Epidemiological studies indicate that hyperuricemia is closely associated with the occurrence of various diseases such as gout and cardiovascular diseases. Currently, the first-line therapeutic medications used to reduce UA levels primarily include xanthine oxidase (XO) inhibitors, which limit UA production, and urate transporter 1 (URAT1) inhibitors, which decrease urate reabsorption and enhance urate excretion. Despite significant progress in urate-lowering therapies, long-term use of these drugs can cause hepatorenal toxicity as well as cardiovascular complications. Therefore, there is an urgent need for novel anti-hyperuricemic agents with better efficacy and lower toxicity. This perspective mainly focuses on the current research progress and design strategy of anti-hyperuricemic agents, particularly those targeting XO and URAT1. It is our hope that this perspective will provide insights into the challenges and opportunities for anti-hyperuricemic drug discovery.