dc.contributor.author | Wu, Hong | en_US |
dc.contributor.author | Wang, Wenchao | en_US |
dc.contributor.author | Liu, Feiyang | en_US |
dc.contributor.author | Weisberg, Ellen L. | en_US |
dc.contributor.author | Tian, Bei | en_US |
dc.contributor.author | Chen, Yongfei | en_US |
dc.contributor.author | Li, Binhua | en_US |
dc.contributor.author | Wang, Aoli | en_US |
dc.contributor.author | Wang, Beilei | en_US |
dc.contributor.author | Zhao, Zheng | en_US |
dc.contributor.author | McMillin, Douglas W. | en_US |
dc.contributor.author | Hu, Chen | en_US |
dc.contributor.author | Li, Hong | en_US |
dc.contributor.author | Wang, Jinhua | en_US |
dc.contributor.author | Liang, Yanke | en_US |
dc.contributor.author | Buhrlage, Sara J. | en_US |
dc.contributor.author | Liang, Junting | en_US |
dc.contributor.author | Liu, Jing | en_US |
dc.contributor.author | Yang, Guang | en_US |
dc.contributor.author | Brown, Jennifer
R. | en_US |
dc.contributor.author | Treon, Steven P. | en_US |
dc.contributor.author | Mitsiades, Constantine S. | en_US |
dc.contributor.author | Griffin, James D. | en_US |
dc.contributor.author | Liu, Qingsong | en_US |
dc.contributor.author | Gray, Nathanael S. | en_US |
dc.date.accessioned | 2015-03-02T17:37:09Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | Wu, 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.issn | 1554-8929 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065302 | |
dc.description.abstract | BTK 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.iso | en_US | en |
dc.publisher | American Chemical
Society | en |
dc.relation.isversionof | doi:10.1021/cb4008524 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027949/pdf/ | en |
dash.license | LAA | en_US |
dc.title | Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | ACS Chemical Biology | en |
dash.depositing.author | Weisberg, Ellen L. | en_US |
dc.date.available | 2015-03-02T17:37:09Z | |
dc.identifier.doi | 10.1021/cb4008524 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Liang, Yanke | |
dash.contributor.affiliated | Yang, Guang | |
dash.contributor.affiliated | Griffin, James | |
dash.contributor.affiliated | Weisberg, Ellen | |
dash.contributor.affiliated | Wang, Jinhua | |
dash.contributor.affiliated | Gray, Nathanael | |
dash.contributor.affiliated | Mitsiades, Constantine | |
dash.contributor.affiliated | Treon, Steven | |