Repurposing fluvoxamine as an inhibitor for NUDT5 in breast cancer cell: an in silico and in vitro study

Sumathi Ramasamy; Kanimozhi Jeyaram; Aathimoolam Narayanan; Sankarganesh Arunachalam; Selvarajan Ethiraj; Muthumanickam Sankar; Boomi Pandian

doi:10.1007/s40203-024-00293-2

Repurposing fluvoxamine as an inhibitor for NUDT5 in breast cancer cell: an in silico and in vitro study

In Silico Pharmacol. 2024 Dec 24;13(1):5. doi: 10.1007/s40203-024-00293-2. eCollection 2025.

Authors

Sumathi Ramasamy¹, Kanimozhi Jeyaram¹, Aathimoolam Narayanan¹, Sankarganesh Arunachalam², Selvarajan Ethiraj³, Muthumanickam Sankar⁴, Boomi Pandian⁴

Affiliations

¹ Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, 626126 Tamil Nadu India.
² Department of Life Sciences, Christ University, Bengaluru, 560029 Karnataka India.
³ Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chennai, 603203 Tamil Nadu India.
⁴ Department of Bioinformatics, Alagappa University, Karaikudi, 630003 Tamil Nadu India.

PMID: 39726906
PMCID: PMC11668718 (available on 2025-12-24)
DOI: 10.1007/s40203-024-00293-2

Abstract

Drug repurposing is necessary to accelerate drug discovery and meet the drug needs. This study investigated the possibility of using fluvoxamine to inhibit the cellular metabolizing enzyme NUDT5 in breast cancer. Computational and experimental techniques were used to evaluate the structural flexibility, binding stability, and chemical reactivity of the drugs. These findings indicated that fluvoxamine effectively suppressed the activity of NUDT5, as evidenced by a binding score of - 8.514 kcal/mol. Furthermore, the binding positions of fluvoxamine and NUDT5 were optimized. Fluvoxamine attachment to the active sites of Trp28, Trp46, Glu47, Arg51, Arg84, and Leu98 in NUDT5 has been shown to alter the metabolism of ADPr. These alterations play a role in ATP production in the breast cancer cells. In addition, an MTT assay conducted on the MCF-7 cell line using fluvoxamine revealed an IC50 value of 53.86 ± 0.05 µM. Fluvoxamine-induced apoptosis was confirmed as evidenced by AO/EtBr and DAPI staining.

Graphical abstract: Effect of fluvoxamine on breast cancer cells.

Keywords: Breast cancer; Drug repurposing; Fluvoxamine; MCF-7.; Molecular dynamic simulation; NUDT5.

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