Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development.
J Med Chem
; 56(14): 5979-83, 2013 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-23808545
ABSTRACT
Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Proteína Supressora de Tumor p53
/
Proteínas Proto-Oncogênicas c-mdm2
/
Para-Aminobenzoatos
/
Antineoplásicos
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos