High-throughput kinase profiling : a more efficient approach toward the discovery of new kinase inhibitors

Miduturu, Chandrasekhar V. and Deng, Xianming and Kwiatkowski, Nicholas and Yang, Wannian and Brault, Laurent and Filippakopoulos, Panagis and Chung, Eunah and Yang, Qingkai and Schwaller, Juerg and Knapp, Stefan and King, Randall W. and Lee, Jiing-Dwan and Herrgard, Sanna and Zarrinkar, Patrick and Gray, Nathanael S.. (2011) High-throughput kinase profiling : a more efficient approach toward the discovery of new kinase inhibitors. Chemistry & biology, Vol. 18, H. 7. pp. 868-879.

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Official URL: http://edoc.unibas.ch/dok/A6004064

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Selective protein kinase inhibitors have only been developed against a small number of kinase targets. Here we demonstrate that "high-throughput kinase profiling" is an efficient method for the discovery of lead compounds for established as well as unexplored kinase targets. We screened a library of 118 compounds constituting two distinct scaffolds (furan-thiazolidinediones and pyrimido-diazepines) against a panel of 353 kinases. A distinct kinase selectivity profile was observed for each scaffold. Selective inhibitors were identified with submicromolar cellular activity against PIM1, ERK5, ACK1, MPS1, PLK1-3, and Aurora A,B kinases. In addition, we identified potent inhibitors for so far unexplored kinases such as DRAK1, HIPK2, and DCAMKL1 that await further evaluation. This inhibitor-centric approach permits comprehensive assessment of a scaffold of interest and represents an efficient and general strategy for identifying new selective kinase inhibitors.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Childhood Leukemia (Schwaller)
UniBasel Contributors:Schwaller, Jürg
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Feb 2014 15:45
Deposited On:27 Feb 2014 15:45

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