國家衛生研究院 NHRI:Item 3990099045/4890
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12189/12972 (94%)
造訪人次 : 967224      線上人數 : 890
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/4890


    題名: Fast-forwarding hit to lead: Aurora and epidermal growth factor receptor kinase inhibitor lead identification
    作者: Coumar, MS;Chu, CY;Lin, CW;Shiao, HY;Ho, YL;Reddy, R;Lin, WH;Chen, CH;Peng, YH;Leou, JS;Lien, TW;Huang, CT;Fang, MY;Wu, SH;Wu, JS;Chittimalla, SK;Song, JS;Hsu, JT;Wu, SY;Liao, CC;Chao, YS;Hsieh, HP
    貢獻者: Division of Biotechnology and Pharmaceutical Research
    摘要: A focused library of furanopyrimidine (350 compounds) was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit 1a was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity in HCT-116 colon cancer cell line. On the basis of docking studies with EGFR hit 1s, introduction of acrylamide Michael acceptor group led to 8, which inhibited both the wild and mutant EGFR kinase and also showed antiproliferative activity in HCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.
    日期: 2010-06-15
    關聯: Journal of Medicinal Chemistry. 2010 Jun 15;53(13):4980-4988.
    Link to: http://dx.doi.org/10.1021/jm1000198
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000279282300015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77954325013
    顯示於類別:[謝興邦] 期刊論文
    [趙宇生(2002-2013)] 期刊論文
    [伍素瑩] 期刊論文
    [徐祖安] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    PUB20550212.pdf2108KbAdobe PDF1062檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

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