Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain.
Bioorg Med Chem Lett
; 21(18): 5605-9, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21788134
ABSTRACT
Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promise for the treatment of human cancers harboring activated Stat3. Herein, we report the design and synthesis of a focused library of salicylic acid containing Stat3 SH2 domain binders. The most potent inhibitor, 17o, effectively disrupted Stat3-phosphopeptide complexes (K(i)=13 µM), inhibited Stat3-Stat3 protein interactions (IC(50)=19 µM) and silenced intracellular Stat3 phosphorylation and Stat3-target gene expression profiles. Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC(50)=10 and 16 µM, respectively).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade da Membrana Celular
/
Domínios de Homologia de src
/
Ácido Salicílico
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Fator de Transcrição STAT3
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article