Novel purine and pyrazolo[3,4-d]pyrimidine inhibitors of PI3 kinase-alpha: Hit to lead studies.
Bioorg Med Chem Lett
; 20(2): 636-9, 2010 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-19969455
ABSTRACT
Series of purine and pyrazolo[3,4-d]pyrimidine inhibitors of phosphatidylinositol-3-kinases (PI3K) have been prepared. The optimized purine inhibitors show good potency in a PI3K p110alpha (PI3K-alpha) fluorescence polarization assay with good selectivity versus PI3K p110gamma (PI3K-gamma) and the mammalian target of rapamycin (mTOR). The related pyrazolo[3,4-d]pyrimidines show potent PI3K-alpha and mTOR inhibition with good selectivity versus PI3K-gamma. Representative compounds showed activity in a cellular proliferation assay against Caco-2 colorectal, LoVo colorectal and PC3MM2 prostate adenocarcinoma cancer cells. Signaling through the PI3K pathway was confirmed via inhibition of phospho-AKT in MDA-361 cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Purinas
/
Pirazóis
/
Piridinas
/
Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos