Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach

Chulho Lee, Jee Sun Yang, Gyoonhee Han

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Article number634
Pages (from-to)1575-1581
Number of pages7
JournalArchives of pharmacal research
Volume38
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1

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Derivatives
fms-Like Tyrosine Kinase 3
Phosphotransferases
Data Mining
Drug Discovery
Acute Myeloid Leukemia
Libraries
Assays
Nitric Oxide
Tumor Necrosis Factor-alpha
thienopyrimidine

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Cite this

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title = "Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach",
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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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 journalArticle

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