Identification of para-Substituted Benzoic Acid Derivatives as Potent Inhibitors of the Protein Phosphatase Slingshot.
ChemMedChem
; 10(12): 1980-7, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26553423
ABSTRACT
Slingshot proteins form a small group of dual-specific phosphatases that modulate cytoskeleton dynamics through dephosphorylation of cofilin and Lim kinases (LIMK). Small chemical compounds with Slingshot-inhibiting activities have therapeutic potential against cancers or infectious diseases. However, only a few Slingshot inhibitors have been investigated and reported, and their cellular activities have not been examined. In this study, we identified two rhodanine-scaffold-based para-substituted benzoic acid derivatives as competitive Slingshot inhibitors. The top compound, (Z)-4-((4-((4-oxo-2-thioxo-3-(o-tolyl)thiazolidin-5-ylidene)methyl)phenoxy)methyl)benzoic acid (D3) had an inhibition constant (Ki) of around 4â
µm and displayed selectivity over a panel of other phosphatases. Moreover, compound D3 inhibited cell migration and cofilin dephosphorylation after nerve growth factor (NGF) or angiotensinâ
II stimulation. Therefore, our newly identified Slingshot inhibitors provide a starting point for developing Slingshot-targeted therapies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Rodanina
/
Benzoatos
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Fosfoproteínas Fosfatases
/
Ácido Benzoico
/
Inibidores Enzimáticos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China