Unveiling the therapeutic role of penfluridol and BMS-754,807: NUDT5 inhibition in breast cancer

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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Main Authors: Majed S. AlFayi, Mohd Saeed, Irfan Ahmad, Mohd Adnan Kausar, Samra Siddiqui, Saba Irem, Faisal Fawaz Alshammari, Riadh Badraoui, Dharmendra Kumar Yadav
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Chemical Physics Impact
Subjects:
Breast Cancer
NUDT5
MD simulation
PCA
FEL
Online Access:http://www.sciencedirect.com/science/article/pii/S2667022425000593
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Summary: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.
ISSN:2667-0224

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