Discovery of highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling

Title
Discovery of highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling
Authors
이상희조아라박승범
Issue Date
2013-01
Publisher
MedChemComm
Citation
VOL 4, NO 1-232
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.
URI
http://pubs.kist.re.kr/handle/201004/67440
ISSN
2040-2503
Appears in Collections:
KIST Publication > Article
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