Structure-based optimization of morpholino-triazines as PI3K and mTOR inhibitors.
Bioorg Med Chem Lett
; 22(2): 1009-13, 2012 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-22197143
ABSTRACT
A virtual screen of our in-house database using various fingerprint techniques returned several triazine hits which were found to be mTOR inhibitors with a slight selectivity over PI3Kα. Using structure-guided lead optimization the inhibitory activity towards mTOR and PI3Kα was increased to the low nanomolar range. Exploiting shape differences in the binding-site allowed for the design of mTOR selective inhibitors. Focus on ligand efficiency ensured the inhibitors retained a low molecular weight and desirable drug-like properties.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triazinas
/
Morfolinas
/
Inhibidores de Proteínas Quinasas
/
Serina-Treonina Quinasas TOR
/
Inhibidores de las Quinasa Fosfoinosítidos-3
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Singapur