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dc.contributor.authorWu, Hongen_US
dc.contributor.authorWang, Wenchaoen_US
dc.contributor.authorLiu, Feiyangen_US
dc.contributor.authorWeisberg, Ellen L.en_US
dc.contributor.authorTian, Beien_US
dc.contributor.authorChen, Yongfeien_US
dc.contributor.authorLi, Binhuaen_US
dc.contributor.authorWang, Aolien_US
dc.contributor.authorWang, Beileien_US
dc.contributor.authorZhao, Zhengen_US
dc.contributor.authorMcMillin, Douglas W.en_US
dc.contributor.authorHu, Chenen_US
dc.contributor.authorLi, Hongen_US
dc.contributor.authorWang, Jinhuaen_US
dc.contributor.authorLiang, Yankeen_US
dc.contributor.authorBuhrlage, Sara J.en_US
dc.contributor.authorLiang, Juntingen_US
dc.contributor.authorLiu, Jingen_US
dc.contributor.authorYang, Guangen_US
dc.contributor.authorBrown, Jennifer R.en_US
dc.contributor.authorTreon, Steven P.en_US
dc.contributor.authorMitsiades, Constantine S.en_US
dc.contributor.authorGriffin, James D.en_US
dc.contributor.authorLiu, Qingsongen_US
dc.contributor.authorGray, Nathanael S.en_US
dc.date.accessioned2015-03-02T17:37:09Z
dc.date.issued2014en_US
dc.identifier.citationWu, H., W. Wang, F. Liu, E. L. Weisberg, B. Tian, Y. Chen, B. Li, et al. 2014. “Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma.” ACS Chemical Biology 9 (5): 1086-1091. doi:10.1021/cb4008524. http://dx.doi.org/10.1021/cb4008524.en
dc.identifier.issn1554-8929en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14065302
dc.description.abstractBTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling and cellular assays to develop a potent, selective, and irreversible BTK kinase inhibitor, QL47, which covalently modifies Cys481. QL47 inhibits BTK kinase activity with an IC50 of 7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with an EC50 of 475 nM, and inhibits phosphorylation of a downstream effector PLCγ2 (Tyr759) with an EC50 of 318 nM. In Ramos cells QL47 induces a G1 cell cycle arrest that is associated with pronounced degradation of BTK protein. QL47 inhibits the proliferation of B-cell lymphoma cancer cell lines at submicromolar concentrations.en
dc.language.isoen_USen
dc.publisherAmerican Chemical Societyen
dc.relation.isversionofdoi:10.1021/cb4008524en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027949/pdf/en
dash.licenseLAAen_US
dc.titleDiscovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphomaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalACS Chemical Biologyen
dash.depositing.authorWeisberg, Ellen L.en_US
dc.date.available2015-03-02T17:37:09Z
dc.identifier.doi10.1021/cb4008524*
dash.authorsorderedfalse
dash.contributor.affiliatedLiang, Yanke
dash.contributor.affiliatedYang, Guang
dash.contributor.affiliatedTreon, Steven
dash.contributor.affiliatedGriffin, James
dash.contributor.affiliatedMitsiades, Constantine
dash.contributor.affiliatedWeisberg, Ellen
dash.contributor.affiliatedWang, Jinhua
dash.contributor.affiliatedGray, Nathanael


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