Identification of Akt pathway inhibitors using redistribution screening on the FLIPR and the IN Cell 3000 analyzer.
J Biomol Screen
; 10(1): 20-9, 2005 Feb.
Article
en En
| MEDLINE
| ID: mdl-15695340
ABSTRACT
The PI3-kinase/Akt pathway is an important cell survival pathway that is deregulated in the majority of human cancers. Despite the apparent druggability of several kinases in the pathway, no specific catalytic inhibitors have been reported in the literature. The authors describe the development of a fluorometric imaging plate reader (FLIPR)-based Akt1 translocation assay to discover inhibitors of Akt1 activation. Screening of a diverse chemical library of 45,000 compounds resulted in identification of several classes of Akt1 translocation inhibitors. Using a combination of classical in vitro assays and translocation assays directed at different steps of the Akt pathway, the mechanisms of action of 2 selected chemical classes were further defined. Protein translocation assays emerge as powerful tools for hit identification and characterization.
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Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Proteínas Proto-Oncogénicas
/
Proteínas Serina-Treonina Quinasas
/
Inhibidores de Proteínas Quinasas
/
Evaluación Preclínica de Medicamentos
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
J Biomol Screen
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2005
Tipo del documento:
Article