Inhibition of Angiogenesis by the Antifungal Drug Itraconazole
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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While screening compounds known to inhibit human endothelial cell proliferation to find angiogenesis inhibitors, Chong and colleagues unexpectedly identified itraconazole as a promising anti-angiogenic agent.
“While screening a collection of compounds known to inhibit human endothelial cell proliferation to find effective angiogenesis inhibitors, Chong and colleagues unexpectedly identified ITZ as a promising anti-angiogenic agent.8”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [8]
A high-throughput screen of the Hopkins Drug Library identified 20 compounds that significantly reduced HIF-1 transcriptional activity, 11 of which were cardiac glycosides, including digoxin, ouabain, proscillaridin A, and digitoxin.
“A high-throughput screen of the Hopkins Drug Library [294] identified 20 compounds that significantly reduced HIF-1 transcriptional activity, 11 of which were cardiac glycosides, including digoxin, ouabain, proscillaridin A, and digitoxin.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [294]
Cites
β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
Rothstein, J. D., Patel, S., Regan, M. R., Haenggeli, C., Huang, Y. H., Bergles, D. E., Jin, L., Dykes Hoberg, M., Vidensky, S., Chung, D. S., et al. (2005) · Nature · doi:10.1038/nature03180 · Cited by 1,518 · see citing works
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Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S.-J., Anders, R. A., Liu, J. O., & Pan, D. (2012) · Genes & Development · doi:10.1101/gad.192856.112 · Cited by 1,452 · see citing works
Self-citationDigoxin and other cardiac glycosides inhibit HIF-1α synthesis and block tumor growth
Zhang, H., Qian, D. Z., Tan, Y. S., Lee, K., Gao, P., Ren, Y. R., Rey, S., Hammers, H., Chang, D., Pili, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809763105 · Cited by 624 · see citing works
Self-citationRecent Advances in Drug Repositioning for the Discovery of New Anticancer Drugs
Shim, J. S., & Liu, J. O. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.9224 · Cited by 382 · see citing works
Self-citationSleire, L., Førde, H. E., Netland, I. A., Leiss, L., Skeie, B. S., & Enger, P. Ø. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.07.013 · Cited by 329 · see citing works
Lee, K., Qian, D. Z., Rey, S., Wei, H., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812801106 · Cited by 289 · see citing works
Self-citationRetractedRepurposing drugs in oncology (ReDO)—Cimetidine as an anti-cancer agent
Pantziarka, P. (2014) · ecancermedicalscience · doi:10.3332/ecancer.2014.485 · Cited by 280 · see citing works
Cholesterol trafficking is required for mTOR activation in endothelial cells
Xu, J., Dang, Y., Ren, Y. R., & Liu, J. O. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910872107 · Cited by 209 · see citing works
Self-citationAntonarakis, E. S., Heath, E. I., Smith, D. C., Rathkopf, D., Blackford, A. L., Danila, D. C., King, S., Frost, A., Ajiboye, A. S., Zhao, M., et al. (2013) · The Oncologist · doi:10.1634/theoncologist.2012-314 · Cited by 180 · see citing works
Liu, R., Li, J., Zhang, T., Zou, L., Chen, Y., Wang, K., Lei, Y., Yuan, K., Li, Y., Lan, J., et al. (2014) · Autophagy · doi:10.4161/auto.28912 · Cited by 178 · see citing works
Repurposing itraconazole as an anticancer agent
Tsubamoto, H., Ueda, T., Inoue, K., Sakata, K., Shibahara, H., & Sonoda, T. (2017) · Oncology Letters · doi:10.3892/ol.2017.6325 · Cited by 107 · see citing works
Head, S. A., Shi, W. Q., Yang, E. J., Nacev, B. A., Hong, S. Y., Pasunooti, K. K., Li, R.-J., Shim, J. S., & Liu, J. O. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.6b00849 · Cited by 82 · see citing works
Self-citationLiang, G., Liu, M., Wang, Q., Shen, Y., Mei, H., Li, D., & Liu, W. (2017) · Oncotarget · doi:10.18632/oncotarget.15324 · Cited by 78 · see citing works
Itraconazole attenuates the stemness of nasopharyngeal carcinoma cells via triggering ferroptosis
Xu, Y., Wang, Q., Li, X., Chen, Y., & Xu, G. (2021) · Environmental Toxicology · doi:10.1002/tox.23031 · Cited by 51 · see citing works
Li, C.-L., Fang, Z.-X., Wu, Z., Hou, Y.-Y., Wu, H.-T., & Liu, J. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113616 · Cited by 46 · see citing works
Self-citationRetractedHIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3 · see citing works
“A high-throughput screen of the Hopkins Drug Library [294] identified 20 compounds that significantly reduced HIF-1 transcriptional activity, 11 of which were cardiac glycosides, including digoxin, ouabain, proscillaridin A, and digitoxin.”
Marzi, M., Ghasemian, A., Ghanbariasad, A., Nournia, E., & Zarenezhad, E. (2026) · RSC Advances · doi:10.1039/d5ra09799a
- Authors
- Chong, C. R., Xu, J., Lu, J., Bhat, S., Sullivan, D. J., & Liu, J. O.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Liu, Jun O.
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-04
- Volume
- 2
- Issue
- 4
- Pages
- 263-270
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- OpenAlex
- W2006333161
- Cited by
- 210
- References
- 1
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 7 · 2023: 11 · 2022: 12 · 2021: 10 · 2020: 20 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 11 · 2015: 10 · 2014: 21 · 2013: 10 · 2012: 8
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- itraconazole, angiogenesis inhibition, antiangiogenic drugs, endothelial cell proliferation, lanosterol 14α-demethylase, drug repurposing, antifungal agents, G1 cell cycle arrest, vascular endothelial growth factor, basic fibroblast growth factor, drug screening
- MeSH terms
- Animals, Antifungal Agents, Cattle, Cell Cycle, Cell Line, Drug Evaluation, Preclinical, Endothelium, Vascular, Female, Humans, Male, Neovascularization, Pathologic, Oxidoreductases, Stereoisomerism, Itraconazole, Jurkat Cells, Angiogenesis Inhibitors, Cell Proliferation, Mice, Sterol 14-Demethylase, Cytochrome P-450 Enzyme Inhibitors
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