國家衛生研究院 NHRI:Item 3990099045/16710
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12500/13673 (91%)
造访人次 : 2597643      在线人数 : 405
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于NHRI ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/16710


    题名: Novel naphthyridones targeting pannexin 1 for colitis management
    作者: Hsueh, WY;Wu, YL;Weng, MT;Liu, SY;Santavanond, JP;Liu, YC;Lin, C;Lai, CN;Lu, YR;Hsu, JY;Gao, HY;Lee, JC;Wei, SC;Lyu, PC;Poon, IKH;Hsieh, HP;Chiu, YH
    贡献者: Institute of Biotechnology and Pharmaceutical Research;Institute of Population Health Sciences
    摘要: Pannexin 1 (PANX1) forms cell-surface channels capable of releasing signaling metabolites for diverse patho-physiological processes. While inhibiting dysregulated PANX1 has been proposed as a therapeutic strategy for many pathological conditions, including inflammatory bowel disease (IBD), low efficacy, or poor specificity of classical PANX1 inhibitors introduces uncertainty for their applications in basic and translational research. Here, hit-to-lead optimization is performed and a naphthyridone, compound 12, is identified as a new PANX1 inhibitor with an IC50 of 0.73 mu m that does not affect pannexin-homologous LRRC8/SWELL1 channels. Using structure-activity relationship analysis, mutagenesis, cell thermal shift assays, and molecular docking, it is revealed that compound 12 directly engages PANX1 Trp74 residue. Using a dextran sodium sulfate mouse model of IBD, it is found that compound 12 markedly reduced colitis severity, highlighting new PANX1 inhibitors as a proof-of-concept treatment for IBD. These data describe the mechanism of action for a new PANX1 inhibitor, uncover the binding site for future drug design, and present a targeted strategy for treating IBD.
    日期: 2024-12-30
    關聯: Advanced Science. 2024 Dec 30;Article in Press.
    Link to: http://dx.doi.org/10.1002/advs.202411538
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2198-3844&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001388330600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85213705839
    显示于类别:[李靜琪] 期刊論文
    [謝興邦] 期刊論文
    [其他] 期刊論文

    文件中的档案:

    档案 描述 大小格式浏览次数
    ISI001388330600001.pdf8871KbAdobe PDF37检视/开启


    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈