Zhang Jiaxin, Hong Liang, Xu Wenfei, Zhang Xin, Fu Huina, Song Xinan, Zhao Jing
Joint Laboratory of Chinese Herbal Glycoengineering and Testing Technology, University of Macau & National Glycoengineering Research Center, Macao, China.
Macao Centre for Testing of Chinese Medicine, University of Macau, Macao, China.
PLoS One. 2025 Aug 13;20(8):e0328559. doi: 10.1371/journal.pone.0328559. eCollection 2025.
Gout, caused by hyperuricemia, has a detrimental impact on patients'quality of life. The urate transporter 1 (URAT1) stands out as a key therapeutic target. However, its clinical development remains uncertain. This study aims to explore the landscape of URAT1 inhibitors by combining global patent analytics with computational drug design. We utilized the Derwent Innovation platform to analyze patents (from 2005 to 2024). Molecular docking was performed on 73.96% of novel compounds using AutoDock Vina. Additionally, scaffold diversity was analyzed using the Bemis-Murcko (BM) scaffold approach. A total of 2,195 entries were screened and eventually narrowed down to 1,056 high-value entries. The global research on URAT1 inhibitors is highly active, with China, the US, Japan, and Europe leading. Most patents are new compounds, indicating significant potential for novel drug development. Molecular docking showed ideal binding affinities for most compounds. The top five BM scaffolds were identified and compared with marketed drugs. This study highlights the potential for developing new URAT1 inhibitors. The identified compounds and scaffolds offer promising starting points for further drug development. Future work should focus on experimental validation and exploring clinical potential.
由高尿酸血症引起的痛风对患者的生活质量有不利影响。尿酸盐转运蛋白1(URAT1)是一个关键的治疗靶点。然而,其临床开发仍不确定。本研究旨在通过结合全球专利分析和计算机辅助药物设计来探索URAT1抑制剂的情况。我们利用德温特创新平台分析专利(2005年至2024年)。使用AutoDock Vina对73.96%的新型化合物进行了分子对接。此外,使用贝米斯-默尔科(BM)支架方法分析了支架多样性。共筛选出2195条记录,最终缩小至1056条高价值记录。全球对URAT1抑制剂的研究非常活跃,中国、美国、日本和欧洲处于领先地位。大多数专利是新化合物,表明新药开发具有巨大潜力。分子对接显示大多数化合物具有理想的结合亲和力。确定了前五种BM支架并与上市药物进行了比较。本研究突出了开发新型URAT1抑制剂的潜力。所确定的化合物和支架为进一步的药物开发提供了有前景的起点。未来的工作应集中在实验验证和探索临床潜力上。