Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors.
Bioorg Med Chem Lett
; 27(5): 1311-1315, 2017 03 01.
Article
en En
| MEDLINE
| ID: mdl-28169164
ABSTRACT
Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pteridinas
/
Diseño de Fármacos
/
Proteínas Proto-Oncogénicas
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
/
Imidazoles
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2017
Tipo del documento:
Article