{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:29:43Z","timestamp":1786685383134,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hyperuricemia (HUA) is primarily driven by hepatic overproduction of urate, mediated by xanthine dehydrogenase (XDH). This preclinical study evaluates YJH\u2010012\u2010D, a\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylgalactosamine (GalNAc)\u2010conjugated small interfering RNA (siRNA) targeting hepatic\n                    <jats:italic>XDH<\/jats:italic>\n                    . Functional assays demonstrated that YJH\u2010012\u2010D potently suppressed both\n                    <jats:italic>XDH<\/jats:italic>\n                    mRNA and protein expression in primary hepatocytes. In mice, a single subcutaneous dose of 8\u2009mg\/kg significantly reduced serum uric acid levels and suppressed hepatic XDH expression for more than 42\u2009days. In cynomolgus monkeys, administration of YJH\u2010012\u2010D at 10\u2009mg\/kg lowered serum uric acid for up to 180\u2009days, with sustained XDH inhibition observed for 120\u2009days. Pharmacokinetic analysis revealed a high liver\u2010to\u2010plasma area under the curve (AUC) ratio (2000\u20136100) and a hepatic half\u2010life exceeding 10\u2009days, consistent with prolonged pharmacological activity. Comprehensive toxicity assessments\u2014including clinical biochemistry, histopathology, and RNA sequencing (RNA\u2010seq)\u2010based off\u2010target profiling\u2014identified no significant adverse effects. Collectively, YJH\u2010012\u2010D exhibits potent, durable urate\u2010lowering efficacy and a favorable safety profile, underscoring its potential as a novel therapeutic candidate for HUA.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70308","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:22:28Z","timestamp":1785558148000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potent and Sustained Lowering of Serum Uric Acid by\n                    <scp>YJH<\/scp>\n                    \u2010012\u2010D, a\n                    <scp>G<\/scp>\n                    al\n                    <scp>NA<\/scp>\n                    c\u2010Conjugated si\n                    <scp>RNA<\/scp>\n                    Targeting Xanthine Dehydrogenase"],"prefix":"10.1002","volume":"14","author":[{"given":"Tingke","family":"Tang","sequence":"first","affiliation":[{"name":"School of International Pharmaceutical Business, China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4823-4952","authenticated-orcid":false,"given":"Qiuying","family":"Li","sequence":"additional","affiliation":[{"name":"Youjia (Hangzhou) Biomedical Technology Co. Ltd  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3547-3678","authenticated-orcid":false,"given":"Chenguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Youjia (Hangzhou) Biomedical Technology Co. Ltd  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Livzon Pharmaceutical Group Inc  Zhuhai Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Livzon Pharmaceutical Group Inc  Zhuhai Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Huang","sequence":"additional","affiliation":[{"name":"Livzon Pharmaceutical Group Inc  Zhuhai Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"He","sequence":"additional","affiliation":[{"name":"Livzon Pharmaceutical Group Inc  Zhuhai Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial People's Hospital  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liang","sequence":"additional","affiliation":[{"name":"General Practice Department Tianjin First Central Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"Youjia (Hangzhou) Biomedical Technology Co. 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