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.

中文翻译：

---

抗高尿酸血症药物的研究进展与展望


体内尿酸（UA 或尿酸盐）的生物合成增加或排泄不足最终导致高尿酸血症的发展。流行病学研究表明，高尿酸血症与痛风、心血管疾病等多种疾病的发生密切相关。目前，用于降低 UA 水平的一线治疗药物主要包括限制 UA 产生的黄嘌呤氧化酶 （XO） 抑制剂和尿酸盐转运蛋白 1 （URAT1） 抑制剂，可减少尿酸盐重吸收并增强尿酸盐排泄。尽管降尿酸治疗取得了重大进展，但长期使用这些药物可导致肝肾毒性以及心血管并发症。因此，迫切需要疗效更好、毒性更低的新型抗高尿酸血症药物。本观点主要关注目前抗高尿酸血症药物的研究进展和设计策略，特别是靶向 XO 和 URAT1 的药物。我们希望这一观点能够为抗高尿酸血症药物发现的挑战和机遇提供见解。