516479-35-9Relevant articles and documents
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
Xu, Jun,Cole, Derek C.,Chang, Chao-Pei Betty,Ayyad, Ramzi,Asselin, Magda,Hao, Wenshan,Gibbons, James,Jelinsky, Scott A.,Saraf, Kathryn A.,Park, Kaapjoo
experimental part, p. 4115 - 4121 (2009/05/27)
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 EC50 of 170 nM. Compound 8 also inhibited cytokine induced JAK activation but did not inhibit BCR-ABL activated STAT5 phosphorylation in K562 cells.