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

Socpus ID

80051927148 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/80051927148

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