English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 848925      Online Users : 1433
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7352


    Title: Optimization of ligand and lipophilic efficiency to identify an in vivo active furano-pyrimidine aurora kinase inhibitor
    Authors: Shiao, HY;Coumar, MS;Chang, CW;Ke, YY;Chi, YH;Chu, CY;Sun, HY;Chen, CH;Lin, WH;Fung, KS;Kuo, PC;Huang, CT;Chang, KY;Lu, CT;Hsu, JT;Chen, CT;Jiaang, WT;Chao, YS;Hsieh, HP
    Contributors: Institute of Biotechnology and Pharmaceutical Research;Institute of Cellular and Systems Medicine
    Abstract: Ligand efficiency (LE) and lipophilic efficiency (LipE) are two important indicators of "drug-likeness", which are dependent on the molecule's activity and physicochemical properties. We recently reported a furano-pyrimidine Aurora kinase inhibitor 4 (LE = 0.25; LipE = 1.75), with potent activity in vitro; however, 4 was inactive in vivo. On the basis of insights obtained from the X-ray co-crystal structure of the lead 4, various solubilizing functional groups were introduced to optimize both the activity and physicochemical properties. Emphasis was placed on identifying potential leads with improved activity as well as better LE and LipE by exercising tight control over the molecular weight and lipophilicity of the molecules. Rational optimization has led to the identification of Aurora kinase inhibitor 27 (IBPR001; LE = 0.26; LipE = 4.78), with improved in vitro potency and physicochemical properties, resulting in an in vivo active (HCT-116 colon cancer xenograft mouse model) anticancer agent.
    Date: 2013-06-28
    Relation: Journal of Medicinal Chemistry. 2013 Jun 28;56(13):5247-5260.
    Link to: http://dx.doi.org/10.1021/jm4006059
    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:000321884200003
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84880175303
    Appears in Collections:[謝興邦] 期刊論文
    [趙宇生(2002-2013)] 期刊論文
    [蔣維棠] 期刊論文
    [陳炯東] 期刊論文
    [徐祖安] 期刊論文
    [紀雅惠] 期刊論文

    Files in This Item:

    File Description SizeFormat
    PUB23808327.pdf4471KbAdobe PDF786View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

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