Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer
Breast cancer (BC) remains a leading cause of cancer-related mortality among women, with hormone-receptor-positive subtypes frequently developing resistance to standard therapies. Nudix hydrolase 5 (NUDT5), an enzyme integral to ADP-ribose metabolism, DNA repair, and hormone-driven transcription, ha...
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Elsevier
2025-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022425000593 |
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| author | Majed S. AlFayi Mohd Saeed Irfan Ahmad Mohd Adnan Kausar Samra Siddiqui Saba Irem Faisal Fawaz Alshammari Riadh Badraoui Dharmendra Kumar Yadav |
| author_facet | Majed S. AlFayi Mohd Saeed Irfan Ahmad Mohd Adnan Kausar Samra Siddiqui Saba Irem Faisal Fawaz Alshammari Riadh Badraoui Dharmendra Kumar Yadav |
| author_sort | Majed S. AlFayi |
| collection | DOAJ |
| description | Breast cancer (BC) remains a leading cause of cancer-related mortality among women, with hormone-receptor-positive subtypes frequently developing resistance to standard therapies. Nudix hydrolase 5 (NUDT5), an enzyme integral to ADP-ribose metabolism, DNA repair, and hormone-driven transcription, has emerged as a promising therapeutic target. This study employed computational drug discovery approaches to identify potential NUDT5 inhibitors from FDA-approved compounds in the Drug-Lib database. Virtual screening and molecular docking revealed four promising candidates: Afacifenacin, Penfluridol, Belaperidone, and BMS-754,807. Detailed molecular dynamics simulations validated their stability, with trajectory analyses, including RMSD, RMSF, and PCA-based free energy landscapes, highlighting consistent and favourable interactions. Among these, BMS-754,807 demonstrated the strongest inhibitory potential, with stable binding, superior hydrogen bonding interactions, and the lowest free energy values. These findings emphasize the therapeutic promise of these compounds, particularly BMS-754,807, in targeting hormone-resistant breast cancer. Future in vitro and in vivo studies will be crucial to confirm these results and advance these inhibitors toward clinical applications. |
| format | Article |
| id | doaj-art-cf104efd019548bfa0fe07d4aa686ff8 |
| institution | DOAJ |
| issn | 2667-0224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-cf104efd019548bfa0fe07d4aa686ff82025-08-20T03:20:05ZengElsevierChemical Physics Impact2667-02242025-06-011010087110.1016/j.chphi.2025.100871Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancerMajed S. AlFayi0Mohd Saeed1Irfan Ahmad2Mohd Adnan Kausar3Samra Siddiqui4Saba Irem5Faisal Fawaz Alshammari6Riadh Badraoui7Dharmendra Kumar Yadav8Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi ArabiaDepartment of Biology, College of Science, University of Hail, Hail Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; Corresponding authors.Department of Biochemistry, College of Medicine, University of Hail, Hail Saudi ArabiaDepartment Health Services Management, College of Public Health and Health Informatics, University of Hail, Hail, Saudi ArabiaSchool of nursing sciences & Allied health, Jamia Hamdard, New DelhiCollege of Medicine, University of Hail, Hail Saudi ArabiaDepartment of Biology, College of Science, University of Hail, Hail Saudi ArabiaDepartment of Biologics, College of Pharmacy, Gachon University, Hambakmoeiro, Yeonsugu, Incheon City 21924, South Korea; Corresponding authors.Breast cancer (BC) remains a leading cause of cancer-related mortality among women, with hormone-receptor-positive subtypes frequently developing resistance to standard therapies. Nudix hydrolase 5 (NUDT5), an enzyme integral to ADP-ribose metabolism, DNA repair, and hormone-driven transcription, has emerged as a promising therapeutic target. This study employed computational drug discovery approaches to identify potential NUDT5 inhibitors from FDA-approved compounds in the Drug-Lib database. Virtual screening and molecular docking revealed four promising candidates: Afacifenacin, Penfluridol, Belaperidone, and BMS-754,807. Detailed molecular dynamics simulations validated their stability, with trajectory analyses, including RMSD, RMSF, and PCA-based free energy landscapes, highlighting consistent and favourable interactions. Among these, BMS-754,807 demonstrated the strongest inhibitory potential, with stable binding, superior hydrogen bonding interactions, and the lowest free energy values. These findings emphasize the therapeutic promise of these compounds, particularly BMS-754,807, in targeting hormone-resistant breast cancer. Future in vitro and in vivo studies will be crucial to confirm these results and advance these inhibitors toward clinical applications.http://www.sciencedirect.com/science/article/pii/S2667022425000593Breast CancerNUDT5MD simulationPCAFEL |
| spellingShingle | Majed S. AlFayi Mohd Saeed Irfan Ahmad Mohd Adnan Kausar Samra Siddiqui Saba Irem Faisal Fawaz Alshammari Riadh Badraoui Dharmendra Kumar Yadav Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer Chemical Physics Impact Breast Cancer NUDT5 MD simulation PCA FEL |
| title | Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer |
| title_full | Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer |
| title_fullStr | Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer |
| title_full_unstemmed | Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer |
| title_short | Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer |
| title_sort | unveiling the therapeutic role of penfluridol and bms 754 807 nudt5 inhibition in breast cancer |
| topic | Breast Cancer NUDT5 MD simulation PCA FEL |
| url | http://www.sciencedirect.com/science/article/pii/S2667022425000593 |
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