Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains

Patrick T. Gunning, William P. Katt, Matthew Glenn, Khandaker Siddique, Joon S. Kim, Richard Jove, Saïd M. Sebti, James Turkson, Andrew D. Hamilton

Research output: Contribution to journalArticle

Abstract

The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC50 value of 31 μM) relative to STAT3 (IC50 value of 560 μM).

Original languageEnglish (US)
Pages (from-to)1875-1878
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number7
DOIs
StatePublished - Apr 1 2007

Keywords

  • Anti-cancer
  • Inhibitors
  • Peptidomimetics
  • SH2 domain recognition
  • STAT1
  • STAT3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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