Discovery of a potent, selective, and orally active human epidermal growth factor receptor-2 sheddase inhibitor for the treatment of cancer.
J Med Chem
; 50(4): 603-6, 2007 Feb 22.
Article
em En
| MEDLINE
| ID: mdl-17256836
ABSTRACT
The design, synthesis, evaluation, and identification of a novel class of (6S,7S)-N-hydroxy-6-carboxamide-5-azaspiro[2.5]octane-7-carboxamides as the first potent and selective inhibitors of human epidermal growth factor receptor-2 (HER-2) sheddase is described. Several compounds were identified that possess excellent pharmacodynamic and pharmacokinetic properties and were shown to decrease tumor size, cleaved HER-2 extracellular domain plasma levels, and potentiate the effects of the humanized anti-HER-2 monoclonal antibody (trastuzumab) in vivo in a HER-2 overexpressing cancer murine xenograft model.
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Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Compostos de Espiro
/
Receptor ErbB-2
/
Amidas
/
Ácidos Hidroxâmicos
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article