Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain
Abbreviated Journal Title
Bioorg. Med. Chem. Lett.
Stat3; Cancer therapeutics; Jak/Stat pathway; Protein-protein; interaction; Inhibitors of apoptosis; SIGNAL TRANSDUCER; GENE-REGULATION; CANCER-CELLS; ACTIVATOR; INHIBITORS; GROWTH; TRANSCRIPTION-3; DIMERIZATION; PROTEIN; ASSAY; Chemistry, Medicinal; Chemistry, Organic
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.
Bioorganic & Medicinal Chemistry Letters
"Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain" (2011). Faculty Bibliography 2010s. 1741.