Identification and characterization of small molecule inhibitors of signal transducer and activator of transcription 3 (STAT3) signaling pathway by virtual screening

Bioorg Med Chem Lett. 2013 Apr 1;23(7):2225-9. doi: 10.1016/j.bmcl.2013.01.056. Epub 2013 Feb 4.

Abstract

Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly-active STAT3. In this study, a series of small molecules were identified as novel inhibitors of STAT3 signaling pathway through virtual screening. A tricyclic scaffold containing compound, 6, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 26.68 μM. In addition, this compound inhibited Tyr705 phosphorylation of STAT3 and had no obvious effect on upstream tyrosine kinases. Thus, compound 6 is a potential lead structure and valuable for further drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Heterocyclic Compounds, 3-Ring / chemical synthesis
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds, 3-Ring
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Small Molecule Libraries