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KMID : 0043320150380091575
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Archives of Pharmacal Research
2015 Volume.38 No. 9 p.1575 ~ p.1581
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Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach
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Lee Chul-Ho
Yang Jee-Sun
Han Gyoon-hee
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Abstract
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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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KEYWORD
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FLT3, Thienopyrimidine, Fragment-based drug design, Text mining, Kinome, Chemical biology
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