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.
| Original language | English |
|---|---|
| Article number | 634 |
| Pages (from-to) | 1575-1581 |
| Number of pages | 7 |
| Journal | Archives of pharmacal research |
| Volume | 38 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2015 Sep 1 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
- Organic Chemistry
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Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach. / Lee, Chulho; Yang, Jee Sun; Han, Gyoonhee.
In: Archives of pharmacal research, Vol. 38, No. 9, 634, 01.09.2015, p. 1575-1581.Research output: Contribution to journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84942194905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942194905&partnerID=8YFLogxK
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 -