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dc.contributor.authorHsu, Kai-Chengen_US
dc.contributor.authorSung, Tzu-Yingen_US
dc.contributor.authorLin, Chih-Taen_US
dc.contributor.authorChiu, Yi-Yuanen_US
dc.contributor.authorHsu, John T. -A.en_US
dc.contributor.authorHung, Hui-Chenen_US
dc.contributor.authorSun, Chung-Mingen_US
dc.contributor.authorBarve, Indrajeeten_US
dc.contributor.authorChen, Wen-Liangen_US
dc.contributor.authorHuang, Wen-Chienen_US
dc.contributor.authorHuang, Chin-Tingen_US
dc.contributor.authorChen, Chun-Hwaen_US
dc.contributor.authorYang, Jinn-Moonen_US
dc.date.accessioned2019-04-03T06:38:46Z-
dc.date.available2019-04-03T06:38:46Z-
dc.date.issued2015-06-16en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://dx.doi.org/10.1038/srep10938en_US
dc.identifier.urihttp://hdl.handle.net/11536/127889-
dc.description.abstractTyrosine kinases regulate various biological processes and are drug targets for cancers. At present, the design of selective and anti-resistant inhibitors of kinases is an emergent task. Here, we inferred specific site-moiety maps containing two specific anchors to uncover a new binding pocket in the C-terminal hinge region by docking 4,680 kinase inhibitors into 51 protein kinases, and this finding provides an opportunity for the development of kinase inhibitors with high selectivity and anti-drug resistance. We present an anchor-based classification for tyrosine kinases and discover two type-C inhibitors, namely rosmarinic acid (RA) and EGCG, which occupy two and one specific anchors, respectively, by screening 118,759 natural compounds. Our profiling reveals that RA and EGCG selectively inhibit 3% (EGFR and SYK) and 14% of 64 kinases, respectively. According to the guide of our anchor model, we synthesized three RA derivatives with better potency. These type-C inhibitors are able to maintain activities for drug-resistant EGFR and decrease the invasion ability of breast cancer cells. Our results show that the type-C inhibitors occupying a new pocket are promising for cancer treatments due to their kinase selectivity and anti-drug resistance.en_US
dc.language.isoen_USen_US
dc.titleAnchor-based classification and type-C inhibitors for tyrosine kinasesen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/srep10938en_US
dc.identifier.journalSCIENTIFIC REPORTSen_US
dc.citation.volume5en_US
dc.citation.spage0en_US
dc.citation.epage0en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.department生物資訊及系統生物研究所zh_TW
dc.contributor.department應用化學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.contributor.departmentDepartment of Applied Chemistryen_US
dc.identifier.wosnumberWOS:000356511700001en_US
dc.citation.woscount3en_US
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