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Issue 1, 2013
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Discovery of a highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling

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Abstract

We discovered a novel molecular framework 4 containing a heterobiaryl pyrazolopyridine moiety as a selective FLT3 kinase inhibitor from phenotype-based viability profiling. Compound 4g showed outstanding selectivity in cellular cytotoxicity against MV-4-11 leukemic cells via the induction of apoptosis. The hypothesis-driven deconvolution elucidated that compound 4g selectively blocked the phosphorylation of FLT3 and its downstream effectors, such as ERK and STAT5, only in MV-4-11 cells. The inhibitory effect of 4g on in vitro enzyme function and FLT3 phosphorylation in cells proved that FLT3 kinase is a direct molecular target of 4g. Finally, the kinase activity profiling of 4g verified its excellent selectivity toward FLT3 over 40 representative kinases, including the receptor tyrosine kinase (RTK) family.

Graphical abstract: Discovery of a highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling

  • This article is part of the themed collection: New Talent
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Publication details

The article was received on 27 Jun 2012, accepted on 09 Sep 2012 and first published on 11 Sep 2012


Article type: Concise Article
DOI: 10.1039/C2MD20169K
Citation: Med. Chem. Commun., 2013,4, 228-232
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    Discovery of a highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling

    S. Lee, A. Jo and S. B. Park, Med. Chem. Commun., 2013, 4, 228
    DOI: 10.1039/C2MD20169K

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