Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma
View/ Open
Author
Wu, Hong
Wang, Wenchao
Liu, Feiyang
Tian, Bei
Chen, Yongfei
Li, Binhua
Wang, Aoli
Wang, Beilei
Zhao, Zheng
McMillin, Douglas W.
Hu, Chen
Li, Hong
Buhrlage, Sara J.
Liang, Junting
Liu, Jing
Brown, Jennifer
R.
Liu, Qingsong
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1021/cb4008524Metadata
Show full item recordCitation
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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027949/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065302
Collections
- FAS Scholarly Articles [18292]
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)