Article(id=1322180289443516646, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322180288214577608, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1623340800000, acceptedDateStr=2021-06-11, onlineDate=1793161945925, onlineDateStr=2026-10-28, pubDate=1630252800000, pubDateStr=2021-08-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793161945925, onlineIssueDateStr=2026-10-28, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793161945925, creator=13701087609, updateTime=1793161945925, updator=13701087609, issue=Issue{id=1322180288214577608, tenantId=1146029695717560320, journalId=1235980733773295621, year='2021', volume='30', issue='16', pageStart='1441', pageEnd='1536', issueExtLink='null', onlineDate='null', pubDate='1630252800000', pubDateStr='2021-08-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793161945632, creator='13701087609', updateTime=1793162101003, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322180940143644721, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322180288214577608, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322180940147839026, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322180288214577608, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1460, endPage=1465, ext={EN=ArticleExt(id=1322180289602900199, articleId=1322180289443516646, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Experimental study of the anti-hyperuricemic effect of compound CC18013, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective: To study the anti-hyperuricemic efficacy, assess the safety of compound CC18013, and explore its possible mechanism related to xanthine oxidase (XOD) inhibition.
Methods: By establishing the acute and chronic hyperuricemic mice models and use of febuxostat as the positive control drug, the effect of CC18013 on serum uric acid levels was detected; the XOD inhibiting ability of CC18013 was determined using in vitro XOD model. The effect of CC18013 on serum and tissue XOD activity in hyperuricemic mice was measured. The interaction between CC18013 and XOD was analyzed by molecular-docking. The body weight change and general state of the mice were observe after a single dose treatment of CC18013.
Results: CC18013 dose-dependently reduced serum uric acid levels in vivo, with the lowest effective dose of 0.5 mg·kg-1. Its IC50 value of XOD inhibition in vitro was 4.6 nmol·L-1. Moreover, it significantly inhibited XOD activity in liver and small intestine. Molecular-docking result indicated that it had a strong interaction with XOD. It showed no evident toxicity under the single dose of 500 mg·kg-1.
Conclusion: CC18013 is an XOD inhibitor with strong anti-hyperuricemic effect and high safety.
, authors=Xue-chen LI
1, Nan JIANG
1, Ya-jun YANG
2, Zhen-xin YAN
1, Lu ZHANG
2, Dong-ting CHEN
1, Jin-ying TIAN
1, Zhi-yan XIAO
2, Fei YE
1, authorsList=Xue-chen LI, Nan JIANG, Ya-jun YANG, Zhen-xin YAN, Lu ZHANG, Dong-ting CHEN, Jin-ying TIAN, Zhi-yan XIAO, Fei YE, authorCompany=null, correspAuthors=Fei YE, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322180289862947048, articleId=1322180289443516646, tenantId=1146029695717560320, journalId=1235980733773295621, language=CN, title=化合物CC18013抗高尿酸血症作用的实验研究, columnId=1236331161786569054, journalTitle=中国新药杂志, columnName=重大新药创制专项巡礼, runingTitle=null, highlight=null, articleAbstract=
目的： 研究化合物CC18013对抗高尿酸血症的药效，评价其早期安全性，并对其与黄嘌呤氧化酶（xanthine oxidase，XOD）活性抑制相关的机制进行探索。
方法： 分别构建急性与慢性高尿酸血症小鼠模型，以非布索坦为阳性对照药，检测不同剂量CC18013对模型动物血尿酸水平的影响。体外酶学方法检测CC18013抑制XOD活性的能力；并观察其对高尿酸血症小鼠血清和组织XOD活性的影响；分子对接分析其与XOD的相互作用。CC18013单次灌胃（ig）给药，观察其对正常ICR小鼠体重增长等一般状态的影响。
结果： 化合物CC18013在体内剂量依赖地发挥降尿酸作用，最低有效剂量为0.5 mg·kg-1。其体外抑制XOD活性的半抑制浓度（IC50）为4.6 nmol·L-1，体内明显降低肝脏与小肠XOD活性。分子对接显示其与XOD存在较强的相互作用。在单次口服（po）500 mg·kg-1剂量下，化合物CC18013对正常ICR小鼠未见明显不良反应。
结论： 化合物CC18013是抗高尿酸血症药效较强且安全性较好的XOD抑制剂。
, authors=李雪晨
1, 姜楠
1, 杨亚军
2, 闫祯昕
1, 张露
2, 陈冬婷
1, 田金英
1, 肖志艳
2, 叶菲
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李雪晨，女，助理研究员，主要从事抗高尿酸血症与肾病药理研究。E-mail：xli@imm.ac.cn。
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李雪晨，女，助理研究员，主要从事抗高尿酸血症与肾病药理研究。E-mail：xli@imm.ac.cn。
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