Abstract
Target identification through chemical biology has been considered one of the most efficient approaches for drug discovery. Thienopyrimidine derivatives were designed to discover potent IκB kinase β (IKKβ) inhibitors based on a known IKKβ inhibitor library. Most of the thienopyrimidine derivatives inhibited nitric oxide and tumor necrosis factor alpha, which are downstream of the NF-κB signaling pathway, but not IKKβ. To identify the appropriate targets of thienopyrimidine analogues, chemical biology approaches, including text mining and a subsequent kinase panel assay from the kinome profiling were used. Based on the results, Fms-like tyrosine kinase 3 was found to be the target for thienopyrimidine derivatives, and was confirmed to be a potent inhibitor for acute myeloid leukemia.
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Acknowledgments
This research was supported by a grant from the Translational Research Center for Protein Function Control (Grant NRF-2009-0083522), the Ministry of Health and Welfare (Grant A120478), the Ministry of Science, ICT and Future Planning (Grant NRF-2013M3A6A4072536), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant NRF-2013R1A1A2008165 and Grant NRF-2015R1A6A3A01020077).
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Lee, C., Yang, J.S. & Han, G. Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach. Arch. Pharm. Res. 38, 1575–1581 (2015). https://doi.org/10.1007/s12272-015-0634-3
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DOI: https://doi.org/10.1007/s12272-015-0634-3