Wu, HongWang, WenchaoLiu, FeiyangWeisberg, EllenTian, BeiChen, YongfeiLi, BinhuaWang, AoliWang, BeileiZhao, ZhengMcMillin, Douglas W.Hu, ChenLi, HongWang, JinhuaLiang, YankeBuhrlage, Sara J.Liang, JuntingLiu, JingYang, GuangBrown, Jennifer R.Treon, StevenMitsiades, ConstantineGriffin, JamesLiu, QingsongGray, Nathanael2015-03-022014Wu, 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/cb4008524.1554-8929http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065302BTK 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-USJournal Article2015-03-0210.1021/cb4008524