Azole-based inhibitors of AKT/PKB for the treatment of cancer.
Bioorg Med Chem Lett
; 20(5): 1559-64, 2010 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-20137943
ABSTRACT
Through a combination of screening and structure-based rational design, we have discovered a series of N(1)-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Azoles
/
Inhibidores de Proteínas Quinasas
/
Proteínas Proto-Oncogénicas c-akt
/
Neoplasias
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos