2-Aminothiadiazole inhibitors of AKT1 as potential cancer therapeutics.
Bioorg Med Chem Lett
; 20(5): 1652-6, 2010 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-20137932
ABSTRACT
A series of 2-aminothiadiazole of inhibitors of AKT1 is described. SAR relationships are discussed, along with selectivity for protein kinase A (PKA) and cyclin-dependent kinase 2 (CDK2). Moderate selectivity observed in several compounds for AKT1 versus PKA is rationalized by X-ray crystallographic analysis. Key compounds showed activity in cellular assays measuring phosphorylation of two AKT substrates, PRAS40 and FKHRL1. Compound 30 was advanced to a mouse liver PD assay, where it showed dose-dependent inhibition of AKT activity, as measured by the inhibition of phospho-PRAS40.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiadiazóis
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Tiazóis
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Inibidores de Proteínas Quinases
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Proteínas Proto-Oncogênicas c-akt
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Isoquinolinas
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Antineoplásicos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos