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.
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Chulho
authors.initials: C
authors.lastname: Lee
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Jee Sun
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea. gyoonhee@yonsei.ac.kr.|Department of Integrated OMICS for Biomedical Sciences (WCU Program), Yonsei University, Seoul, 120-749, Republic of Korea. gyoonhee@yonsei.ac.kr.
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; C476003:thienopyrimidine; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: Chemical biology; FLT3; Fragment-based drug design; Kinome; Text mining; Thienopyrimidine