TY - JOUR
T1 - Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach
AU - Lee, Chulho
AU - Yang, Jee Sun
AU - Han, Gyoonhee
N1 - Publisher Copyright:
© 2015 The Pharmaceutical Society of Korea.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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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U2 - 10.1007/s12272-015-0634-3
DO - 10.1007/s12272-015-0634-3
M3 - Article
C2 - 26186885
AN - SCOPUS:84942194905
VL - 38
SP - 1575
EP - 1581
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
SN - 0253-6269
IS - 9
M1 - 634
ER -