Drug repurposing of 6-AZA-UTP and itraconazole reveals novel B3GALT5 inhibitors for pancreatic cancer.

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.