Tumor-targeting of EGFR inhibitors by hypoxia-mediated activation.
Angew Chem Int Ed Engl
; 53(47): 12930-12935, 2014 Nov 17.
Article
em En
| MEDLINE
| ID: mdl-25079700
ABSTRACT
The development of receptor tyrosine-kinase inhibitors (TKIs) was a major step forward in cancer treatment. However, the therapy with TKIs is limited by strong side effects and drug resistance. The aim of this study was the design of novel epidermal growth factor receptor (EGFR) inhibitors that are specifically activated in malignant tissue. Thus, a Co(III) -based prodrug strategy for the targeted release of an EGFR inhibitor triggered by hypoxia in the solid tumor was used. New inhibitors with chelating moieties were prepared and tested for their EGFR-inhibitory potential. The most promising candidate was coupled to Co(III) and the biological activity tested in cell culture. Indeed, hypoxic activation and subsequent EGFR inhibition was proven. Finally, the compound was tested in vivo, also revealing potent anticancer activity.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Cobalto
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Inibidores de Proteínas Quinases
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Receptores ErbB
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Hipóxia
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Neoplasias Experimentais
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2014
Tipo de documento:
Article