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dc.contributor.authorCoumar, Mohane Selvarajen_US
dc.contributor.authorChu, Chang-Yingen_US
dc.contributor.authorLin, Cheng-Weien_US
dc.contributor.authorShiao, Hui-Yien_US
dc.contributor.authorHo, Yun-Lungen_US
dc.contributor.authorReddy, Randheeren_US
dc.contributor.authorLin, Wen-Hsingen_US
dc.contributor.authorChen, Chun-Hwaen_US
dc.contributor.authorPeng, Yi-Huien_US
dc.contributor.authorLeou, Jiun-Shyangen_US
dc.contributor.authorLien, Tzu-Wenen_US
dc.contributor.authorHuang, Chin-Tingen_US
dc.contributor.authorFang, Ming-Yuen_US
dc.contributor.authorWu, Szu-Hueien_US
dc.contributor.authorWu, Jian-Sungen_US
dc.contributor.authorChittimalla, Santhosh Kumaren_US
dc.contributor.authorSong, Jen-Shinen_US
dc.contributor.authorHsu, John T. -A.en_US
dc.contributor.authorWu, Su-Yingen_US
dc.contributor.authorLiao, Chun-Chenen_US
dc.contributor.authorChao, Yu-Shengen_US
dc.contributor.authorHsieh, Hsing-Pangen_US
dc.date.accessioned2014-12-08T15:06:34Z-
dc.date.available2014-12-08T15:06:34Z-
dc.date.issued2010-07-08en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://dx.doi.org/10.1021/jm1000198en_US
dc.identifier.urihttp://hdl.handle.net/11536/5143-
dc.description.abstractA 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 la 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 Is, 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.en_US
dc.language.isoen_USen_US
dc.titleFast-Forwarding Hit to Lead: Aurora and Epidermal Growth Factor Receptor Kinase Inhibitor Lead Identificationen_US
dc.typeArticleen_US
dc.identifier.doi10.1021/jm1000198en_US
dc.identifier.journalJOURNAL OF MEDICINAL CHEMISTRYen_US
dc.citation.volume53en_US
dc.citation.issue13en_US
dc.citation.spage4980en_US
dc.citation.epage4988en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000279282300015-
dc.citation.woscount27-
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