Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem Biol 2007 Apr 24;2(4):263-70
Date
04/17/2007Pubmed ID
17432820DOI
10.1021/cb600362dScopus ID
2-s2.0-34248598317 (requires institutional sign-in at Scopus site) 183 CitationsAbstract
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.
Author List
Chong CR, Xu J, Lu J, Bhat S, Sullivan DJ Jr, Liu JOMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Antifungal Agents
Cattle
Cell Cycle
Cell Line
Cell Proliferation
Cytochrome P-450 Enzyme Inhibitors
Drug Evaluation, Preclinical
Endothelium, Vascular
Female
Humans
Itraconazole
Jurkat Cells
Male
Mice
Neovascularization, Pathologic
Oxidoreductases
Stereoisomerism
Sterol 14-Demethylase
