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Targeting Protein–Protein Interactions: Suppression of Stat3 Dimerization with Rationally Designed Small‐Molecule, Nonpeptidic SH2 Domain Binders
Author(s) -
Gunning Patrick T.,
Glenn Matthew P.,
Siddiquee Khandaker A. Z.,
Katt William P.,
Masson Eric,
Sebti Saïd M.,
Turkson James,
Hamilton Andrew D.
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800291
Subject(s) - peptidomimetic , small molecule , chemistry , sh2 domain , thiazole , oxazole , stat3 , in vitro , combinatorial chemistry , biophysics , stereochemistry , biochemistry , peptide , signal transduction , biology , receptor tyrosine kinase
Stat3 Inhibition : Rational design of small‐molecule inhibitors of Stat3 dimerization that disrupt Stat3‐mediated cell proliferation pathways are reported here. Suitably substituted oxazole and thiazole scaffolds, derived from peptidomimetic leads, disrupted Stat3:Stat3–DNA‐binding activity in vitro at low‐μ M concentrations, but showed low affinity to the unphosphorylated Stat3 monomer.