Inhibition of angiogenesis by the antifungal drug itraconazole.
ACS Chem Biol
; 2(4): 263-70, 2007 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-17432820
ABSTRACT
Angiogenesis, the formation of new blood vessels, is implicated in a number of important human diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis. To identify clinically useful angiogenesis inhibitors, we assembled and screened a library of mostly Food and Drug Administration-approved drugs for inhibitors of human endothelial cell proliferation. One of the most promising and unexpected hits was itraconazole, a known antifungal drug. Itraconazole inhibits endothelial cell cycle progression at the G1 phase in vitro and blocks vascular endothelial growth factor/basic fibroblast growth factor-dependent angiogenesis in vivo. In attempts to delineate the mechanism of action of itraconazole, we found that human lanosterol 14alpha-demethylase (14DM) is essential for endothelial cell proliferation and may partially mediate the inhibition of endothelial cells by itraconazole. Together, these findings suggest that itraconazole has the potential to serve as an antiangiogenic drug and that lanosterol 14DM is a promising new target for discovering new angiogenesis inhibitors.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Itraconazol
/
Inibidores da Angiogênese
/
Antifúngicos
/
Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos