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

    Authors

    P. T. Gunning; W. P. Katt; M. Glenn; K. Siddique; J. S. Kim; R. Jove; S. M. Sebti; J. Turkson;A. D. Hamilton

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Bioorg. Med. Chem. Lett.

    Keywords

    STAT1; STAT3; peptidomimetics; inhibitors; anti-cancer; SH2 domain; recognition; SIGNAL TRANSDUCER; MOLECULAR TARGETS; GENE-REGULATION; ACTIVATOR; DNA; PATHWAY; Chemistry, Medicinal; Chemistry, Organic

    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 mu M) relative to STAT3 (IC50 value of 560 mu M). (c) 2007 Published by Elsevier Ltd.

    Journal Title

    Bioorganic & Medicinal Chemistry Letters

    Volume

    17

    Issue/Number

    7

    Publication Date

    1-1-2007

    Document Type

    Article

    Language

    English

    First Page

    1875

    Last Page

    1878

    WOS Identifier

    WOS:000245827900008

    ISSN

    0960-894X

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