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Inhibition of the signal transducer and activator of transcription-3 (STAT3) signaling pathway by 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid esters.

Abstract：

:The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4 as a potential STAT3 pathway inhibitor. Optimization of this HTS hit led to the identification of the 7-cyano analogue 8, which inhibited STAT3-Y705 phosphorylation with an EC 50 of 170 nM. Compound 8 also inhibited cytokine induced JAK activation but did not inhibit BCR-ABL activated STAT5 phosphorylation in K562 cells.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Xu J,Cole DC,Chang CP,Ayyad R,Asselin M,Hao W,Gibbons J,Jelinsky SA,Saraf KA,Park K

doi

10.1021/jm701271y

subject

Has Abstract

pub_date

2008-07-24 00:00:00

pages

4115-21

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

51

pub_type

杂志文章

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