Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 21, Issue 18, Pages 5605-5609Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.06.056
Keywords
Stat3; Cancer therapeutics; Jak/Stat pathway; Protein-protein interaction; Inhibitors of apoptosis
Categories
Funding
- NSERC
- University of Toronto
- Canadian Foundation for Innovation
- National Cancer Institute [CA106439, CA128865]
- Ontario Graduate Schoralship
Ask authors/readers for more resources
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 mu M), inhibited Stat3-Stat3 protein interactions (IC(50) = 19 mu M) 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 mu M, respectively). (C) 2011 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available