Title

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

Authors

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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