123rd General Meeting of the KCS

Type Poster Presentation
Area Life Chemistry
Room No. Exhibition Hall 2
Time 4월 19일 (금요일) 11:00~12:30
Code LIFE.P-348
Subject Screeing and characterization of MAP kinase-interacting kinase 1(MNK1) using homogeneous time-resolved fluorescence resonance energy transfer (TR-FRET)
Authors Donghee Kim, Jinho Lee*, Victor Sukbong Hong*
Department of Chemistry, Keimyung University, Korea
Abstract MAP kinase-interacting kinase 1 (MNK1) is a serine/threonine-protein kinase that regulates protein synthesis by phosphorylating eukaryotic translation initiation factor 4E (eIF4E). Overexpression of eIF4E has been reported to play a major role in the development of various cancers such as breast, colon, prostate, head and neck, kidney and lung. Therefore, MNK1 has drawn attention as an important target for cancer treatment. Using the TR-FRET assay method, we performed screening of a kinase focused library 333 compounds at 10 μM concentration and found a series compounds that effectively inhibited the activity MNK1. It was found that 4-substituted-2-amino pyrimidine structures were common cores in these hits. The Lineweaver-Burk double-reciprocal plot and Nonlinear regression analysis of KMU010348, the most potent inhibitor of MNK1 inhibition, revealed that this compound is a competitive inhibitor of ATP.
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