Drug repurposing of 6-AZA-UTP and itraconazole reveals novel B3GALT5 inhibitors for pancreatic cancer
Abstract
Pancreatic cancer has a poor prognosis with limited therapeutic options, necessitating novel treatment strategies. While B3GALT5 enzyme overexpression has been reported in pancreatic cancer cases, effective mechanisms to suppress its activity remain unexplored. In this study, we utilized bioinformatics and in silico studies to evaluate the relationship between B3GALT5 enzyme and pancreatic cancer. Through molecular docking analysis, FDA-approved drugs 6-AZA-UTP and itraconazole were identified as potential B3GALT5 enzyme inhibitors. Biological evaluation on MIA PaCa-2 and AsPC-1 pancreatic cancer cell lines demonstrated that both compounds significantly reduced cell viability. Flow cytometry analysis revealed that both drugs effectively suppressed B3GALT5 enzyme activation by decreasing SSEA-3 expression. Furthermore, both compounds exhibited potent anti-tumor effects by inhibiting cell adhesion, colony formation, and migration while inducing apoptosis in pancreatic cancer cells. Notably, both drugs demonstrated favorable ADMET profiles with no carcinogenic or toxic effects. Our investigations revealed that 6-AZA-UTP and itraconazole can effectively suppress B3GALT5 enzyme activity, resulting in tumor suppression and metastasis inhibition. These findings suggest that either 6-AZA-UTP or itraconazole can inhibit B3GALT5 enzyme activity and may serve as promising therapeutic options for pancreatic cancer treatment through drug repurposing strategy.
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Both 6-AZA-UTP and ITZ demonstrated strong anti-tumor actions by causing pancreatic cancer cells to undergo apoptosis and preventing cell adhesion, colony formation, and migration.
“Additionally, both substances demonstrated strong anti-tumor actions by causing pancreatic cancer cells to undergo apoptosis and preventing cell adhesion, colony formation, and migration.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
Both 6-AZA-UTP and ITZ inhibited activation of the B3GALT5 enzyme by reducing SSEA-3 expression.
“By reducing SSEA-3 expression, both medications successfully inhibited the activation of the B3GALT5 enzyme, according to flow cytometry data.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
In pancreatic cancer cell lines AsPC-1 and MIA PaCa-2, both 6-AZA-UTP and ITZ markedly decreased cell viability.
“According to biological testing on pancreatic cancer cell lines AsPC-1 and MIA PaCa-2, both substances markedly decreased cell viability.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
6-AZA-UTP and ITZ were found to be putative inhibitors of the B3GALT5 enzyme using molecular docking research.
“FDA-approved medications 6-AZA-UTP and ITZ were found to be putative inhibitors of the B3GALT5 enzyme using molecular docking research.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
Neither 6-AZA-UTP nor ITZ had harmful or carcinogenic effects, and both showed good ADMET profiles.
“Notably, neither medication had any harmful or carcinogenic effects and showed good absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
ITZ and 6-AZA-UTP can efficiently decrease the activity of the B3GALT5 enzyme, which suppresses tumors and prevents metastases.
“According to studies, ITZ and 6-AZA-UTP can efficiently decrease the activity of the B3GALT5 enzyme, which suppresses tumors and prevents metastases.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
ITZ or 6-AZA-UTP could be useful therapeutic alternatives for treating pancreatic cancer by repurposing existing drugs.
“These results imply that ITZ or 6-AZA-UTP can both suppress the activity of the B3GALT5 enzyme and could be useful therapeutic alternatives for treating pancreatic cancer by repurposing existing drugs.82”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [82]
Cites
Daina, A., Michielin, O., & Zoete, V. (2017) · Scientific Reports · doi:10.1038/srep42717 · Cited by 18,367 · see citing works
A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer
Neoptolemos, J. P., Stocken, D. D., Friess, H., Bassi, C., Dunn, J., Hickey, H., Beger, H. G., Fernández‐Cruz, L., Dervenis, C., LACAINE, F., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032295 · Cited by 2,709 · see citing works
Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver
Costa-Silva, B., Aiello, N. M., Ocean, A. J., Singh, S., Zhang, H., Thakur, B. K., Becker, A., Hoshino, A., Mark, M. T., Molina, H., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3169 · Cited by 2,692 · see citing works
Ryan, D. P., Hong, T. S., & Bardeesy, N. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1404198 · Cited by 2,348 · see citing works
Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors
Rawla, P., Sunkara, T., & Gaduputi, V. (2019) · World Journal of Oncology · doi:10.14740/wjon1166 · Cited by 2,269 · see citing works
Receptor–ligand molecular docking
Guedes, I. A., de Magalhães, C. S., & Dardenne, L. E. (2013) · Biophysical Reviews · doi:10.1007/s12551-013-0130-2 · Cited by 611 · see citing works
The Clinical Pharmacokinetics of Itraconazole: An Overview
Heykants, J., Peer, A. V., de Velde, V. V., Rooy, P. V., Meuldermans, W., Lavrijsen, K., Woestenborghs, R., Cutsem, J. V., & Cauwenbergh, G. F. M. J. (1989) · Mycoses · doi:10.1111/j.1439-0507.1989.tb02296.x · Cited by 405 · see citing works
Functional Role of Glycosphingolipids in Cell Recognition and Signaling
Hakomori, S., & Igarashi, Y. (1995) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a124992 · Cited by 395 · see citing works
Employing Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer
Halbrook, C. J., & Lyssiotis, C. A. (2017) · Cancer Cell · doi:10.1016/j.ccell.2016.12.006 · Cited by 394 · see citing works
The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice
Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., Alagesan, B., Lee, E. J., Yao, M. A., Lucito, M. S., et al. (2019) · Science · doi:10.1126/science.aaw3145 · Cited by 283 · see citing works
Editorial: In silico Methods for Drug Design and Discovery
Brogi, S., Ramalho, T. C., Kuča, K., Medina‐Franco, J. L., & Valko, M. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.00612 · Cited by 280 · see citing works
Heterocyclic Scaffolds: Centrality in Anticancer Drug Development
Ali, I., Lone, M., ALOthman, Z. A., Al‐Warthan, A., & Sanagi, M. (2015) · Current Drug Targets · doi:10.2174/1389450116666150309115922 · Cited by 257 · see citing works
Anti-cancer Nitrogen-Containing Heterocyclic Compounds
Hosseinzadeh, Z., Ramazani, A., & Razzaghi‐Asl, N. (2018) · Current Organic Chemistry · doi:10.2174/1385272822666181008142138 · Cited by 188 · see citing works
Antonarakis, 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
Repurposing Drugs in Oncology (ReDO)—itraconazole as an anti-cancer agent
Pantziarka, P. (2015) · ecancermedicalscience · doi:10.3332/ecancer.2015.521 · Cited by 165 · see citing works
Molecular Docking for Drug Discovery and Development: A Widely Used Approach but Far from Perfect
Wang, G., & Zhu, W. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0143 · Cited by 153 · see citing works
Isshiki, S., Togayachi, A., Kudo, T., Nishihara, S., Watanabe, M., Kubota, T., Kitajima, M., Shiraishi, N., Sasaki, K., Andoh, T., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.18.12499 · Cited by 146 · see citing works
Ho, T. T. B., Nasti, A., Seki, A., Komura, T., Inui, H., Kozaka, T., Kitamura, Y., Shiba, K., Yamashita, T., Yamashita, T., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001367 · Cited by 112 · see citing works
Loss of ATM accelerates pancreatic cancer formation and epithelial–mesenchymal transition
Russell, R., Perkhofer, L., Liebau, S., Lin, Q., Lechel, A., Feld, F. M., Hessmann, E., Gaedcke, J., Güthle, M., Zenke, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms8677 · Cited by 109 · see citing works
Effects of Antifungal Agents and Interferon on Macrophage Cytotoxicity for Fungi and Tumor Cells
Perfect, J. R., Granger, D. L., & Durack, D. T. (1987) · The Journal of Infectious Diseases · doi:10.1093/infdis/156.2.316 · Cited by 87 · see citing works
Oxygen- and Sulphur-Containing Heterocyclic Compounds as Potential Anticancer Agents
Sachdeva, H., Khaturia, S., Saquib, M., Khatik, N., Khandelwal, A. R., Meena, R., & Sharma, K. (2022) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-022-04099-w · Cited by 81 · see citing works
Aljahdali, M. O., Molla, M. H. R., & Ahammad, F. (2021) · Marine Drugs · doi:10.3390/md19050253 · Cited by 79 · see citing works
Hänggi, K., Vasilikos, L., Valls, A. F., Yerbes, R., Knop, J., Spilgies, L. M., Rieck, K., Misra, T., Bertin, J., Gough, P. J., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.20 · Cited by 78 · see citing works
Cheung, S. K. C., Chuang, P.-K., Huang, H.-W., Hwang‐Verslues, W. W., Cho, C. H.-H., Yang, W., Shen, C., Hsiao, M., Hsu, T.-L., Chang, C., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522602113 · Cited by 74 · see citing works
Self-citationRepurposing itraconazole for the treatment of cancer
Pounds, R., Leonard, S. M., Dawson, W. O., & Kehoe, S. T. (2017) · Oncology Letters · doi:10.3892/ol.2017.6569 · Cited by 67 · see citing works
Pulmonary metastases in pancreatic cancer, is there a survival influence?
Deeb, A., Haque, S., & Olowokure, O. O. (2015) · PubMed Central · doi:10.3978/j.issn.2078-6891.2014.114 · Cited by 58 · see citing works
Kuo, H.-H., Lin, R., Hung, J., Hsieh, C.-B., Hung, T., Lo, F., Ho, M., Yeh, C., Huang, Y., Yu, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11136-w · Cited by 55 · see citing works
Jacobson, K. A., Costanzi, S., Ivanov, A. A., Tchilibon, S., Besada, P., Gao, Z., Maddileti, S., & Harden, T. K. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.11.010 · Cited by 55 · see citing works
In Silico Methods for Drug Design and Discovery
Brogi, S., Ramalho, T. C., Kuca, K., Medina-Franco, J. L., & Valko, M. (2020) · Frontiers research topics · doi:10.3389/978-2-88966-057-5 · Cited by 52 · see citing works
Molla, M. H. R., Aljahdali, M. O., Sumon, M. A. A., Asseri, A. H., Altayb, H. N., Islam, M. S., Alsaiari, A. A., Opo, F. A. D. M., Jahan, N., Ahammad, F., et al. (2023) · Pharmaceuticals · doi:10.3390/ph16010120 · Cited by 45 · see citing works
Lin, C.-W., Wang, Y.-J., Lai, T.-Y., Hsu, T.-L., Han, S.-Y., Wu, H., Shen, C., Dang, V., Chen, M. W., Chen, L.-B., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2114774118 · Cited by 36 · see citing works
Nagaraj, S., Manivannan, S., & Narayan, S. (2021) · Journal of Basic Microbiology · doi:10.1002/jobm.202100204 · Cited by 35 · see citing works
Yasir, M., Park, J., Han, E., Park, W. S., Han, J., Kwon, Y.-S., Lee, H. J., & Chun, W. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01090 · Cited by 34 · see citing works
Glycosylation as a regulator of site-specific metastasis
Bindeman, W. E., & Fingleton, B. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-10015-1 · Cited by 33 · see citing works
Role of tumor cell sialylation in pancreatic cancer progression
Marciel, M. P., Haldar, B., Hwang, J., Bhalerao, N., & Bellis, S. L. (2022) · Advances in cancer research · doi:10.1016/bs.acr.2022.07.003 · Cited by 30 · see citing works
Liao, Y., Wang, Y., Hung, J., Lin, Y., Huang, Y., Liao, G., Hsu, Y., Wu, J.-C., & Yu, A. L.-T. (2021) · Breast Cancer Research · doi:10.1186/s13058-020-01381-9 · Cited by 29 · see citing works
Pancreatic Cancer: Current Status and Challenges
Muñoz, A. R., Chakravarthy, D., Gong, J., Halff, G. A., Ghosh, R., & Kumar, A. P. (2017) · Current Pharmacology Reports · doi:10.1007/s40495-017-0112-3 · Cited by 27 · see citing works
Global trends in pancreas cancer among Asia-Pacific population
Ranganath, R., & Chu, Q. (2021) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-20-118 · Cited by 27 · see citing works
Killing the “BAD”: Challenges for immunotherapy in pancreatic cancer
Li, T., Wang, W., Yu, X., & Liu, L. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188384 · Cited by 26 · see citing works
Itraconazole inhibits proliferation of pancreatic cancer cells through activation of Bak‐1
Jiang, F., Xing, H., Chen, W., Du, J., Ruan, Y., Lin, A., & Zhou, C. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27719 · Cited by 23 · see citing works
Oselusi, S. O., Egieyeh, S. A., & Christoffels, A. G. (2021) · Molecules · doi:10.3390/molecules26123674 · Cited by 18 · see citing works
Serum Level of Long Noncoding RNA B3GALT5-AS1 as a Diagnostic Biomarker of Colorectal Cancer
Ding, Y., Feng, W., Ge, J.-K., Dai, L., Liu, T., Hua, X.-Y., Xu, L., Ju, S., & Yu, J. (2020) · Future Oncology · doi:10.2217/fon-2019-0820 · Cited by 15 · see citing works
6-Azauridine Induces Autophagy-Mediated Cell Death via a p53- and AMPK-Dependent Pathway
Cha, Y.-E., Park, R., Jang, M., Park, Y., Yamamoto, A., Oh, W. K., Lee, E., & Park, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062947 · Cited by 15 · see citing works
In Silico Databases and Tools for Drug Repurposing
Serçinoğlu, O., & Özbek, P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816125-8.00024-9 · Cited by 14 · see citing works
Geme, J. W. S., Martin, H. L., & Davis, C. W. C. (1975) · Infection and Immunity · doi:10.1128/iai.11.5.915-918.1975 · Cited by 2 · see citing works
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Marzi, M., Ghasemian, A., Ghanbariasad, A., Nournia, E., & Zarenezhad, E. (2026) · RSC Advances · doi:10.1039/d5ra09799a
- Authors
- Botcha, L., Sehar, M., Cheng, Y.-C., Zhang, S.-C., Khan Jadoon, M. S., & Chuang, P.-K.
- Affiliations
- National Sun Yat-sen University (TW)
- Corresponding author
- Chuang, Po-Kai
- Venue
- Bioorganic Chemistry
- Publisher
- Elsevier BV
- Published
- 2025-06
- Volume
- 160
- Pages
- 108464
- ISSN
- 0045-2068 (ISSN-L)
- OpenAlex
- W4409328910
- Cited by
- 1
- References
- 45
- Citations by year
- 2026: 1
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Bioorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science and Technology Council (NSTC 113-2320-B-110-012)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- drug repurposing, pancreatic cancer, 6-azauridine, itraconazole, enzyme inhibitors, SSEA-3, apoptosis, metastasis suppression, cell adhesion, cell migration, ADMET properties, MIA PaCa-2 cells, AsPC-1
- MeSH terms
- Antineoplastic Agents, Cell Movement, Cell Survival, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Enzyme Inhibitors, Galactosyltransferases, Humans, Pancreatic Neoplasms, Structure-Activity Relationship, Molecular Structure, Apoptosis, Itraconazole, Cell Line, Tumor, Cell Proliferation, Drug Repositioning, Molecular Docking Simulation
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