Title
Identification Of A Non-Phosphorylated, Cell Permeable, Small Molecule Ligand For The Stat3 Sh2 Domain
Keywords
Cancer therapeutics; Inhibitors of apoptosis; Jak/Stat pathway; Protein-protein interaction; Stat3
Abstract
Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promise for the treatment of human cancers harboring activated Stat3. Herein, we report the design and synthesis of a focused library of salicylic acid containing Stat3 SH2 domain binders. The most potent inhibitor, 17o, effectively disrupted Stat3-phosphopeptide complexes (K i = 13 μM), inhibited Stat3-Stat3 protein interactions (IC 50 = 19 μM) and silenced intracellular Stat3 phosphorylation and Stat3-target gene expression profiles. Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC 50 = 10 and 16 μM, respectively). © 2011 Elsevier Ltd. All rights reserved.
Publication Date
9-15-2011
Publication Title
Bioorganic and Medicinal Chemistry Letters
Volume
21
Issue
18
Number of Pages
5605-5609
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1016/j.bmcl.2011.06.056
Copyright Status
Unknown
Socpus ID
80051927148 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/80051927148
STARS Citation
Page, Brent D.G.; Fletcher, Steven; Yue, Peibin; Li, Zhihua; and Zhang, Xiaolei, "Identification Of A Non-Phosphorylated, Cell Permeable, Small Molecule Ligand For The Stat3 Sh2 Domain" (2011). Scopus Export 2010-2014. 2861.
https://stars.library.ucf.edu/scopus2010/2861