1. Academic Validation
  2. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity

Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity

  • Proc Natl Acad Sci U S A. 2007 May 1;104(18):7391-6. doi: 10.1073/pnas.0609757104.
Khandaker Siddiquee 1 Shumin Zhang Wayne C Guida Michelle A Blaskovich Benjamin Greedy Harshani R Lawrence M L Richard Yip Richard Jove Mark M McLaughlin Nicholas J Lawrence Said M Sebti James Turkson
Affiliations

Affiliation

  • 1 BioMolecular Science Center, University of Central Florida, Orlando, FL 32826, USA.
Abstract

S3I-201 (NSC 74859) is a chemical probe inhibitor of STAT3 activity, which was identified from the National Cancer Institute chemical libraries by using structure-based virtual screening with a computer model of the STAT3 SH2 domain bound to its STAT3 phosphotyrosine peptide derived from the x-ray crystal structure of the Stat3beta homodimer. S3I-201 inhibits STAT3.STAT3 complex formation and STAT3 DNA-binding and transcriptional activities. Furthermore, S3I-201 inhibits growth and induces Apoptosis preferentially in tumor cells that contain persistently activated STAT3. Constitutively dimerized and active Stat3C and STAT3 SH2 domain rescue tumor cells from S3I-201-induced Apoptosis. Finally, S3I-201 inhibits the expression of the Stat3-regulated genes encoding cyclin D1, Bcl-xL, and Survivin and inhibits the growth of human breast tumors in vivo. These findings strongly suggest that the antitumor activity of S3I-201 is mediated in part through inhibition of aberrant STAT3 activation and provide the proof-of-concept for the potential clinical use of STAT3 inhibitors such as S3I-201 in tumors harboring aberrant STAT3.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15146
    98.64%, STAT3 Inhibitor