This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Open AccessArticle
Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy
by
Nahlah Makki Almansour
Nahlah Makki Almansour
Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi Arabia
Int. J. Mol. Sci. 2025, 26(17), 8465; https://doi.org/10.3390/ijms26178465 (registering DOI)
Submission received: 7 July 2025
/
Revised: 26 August 2025
/
Accepted: 27 August 2025
/
Published: 30 August 2025
Abstract
Carbonic anhydrase IX (CA IX) is a transmembrane metalloenzyme that is increased in tumor cells under hypoxia and plays an important role in solid tumor acidification. It is a marker of tumor hypoxia and a prognostic factor in human malignancies. Given the critical role of CA IX and their over expression in many cancer tissues, they have emerged as a promising target for developing novel anticancer therapeutics. In this study we designed a pharmacophore model based on known inhibitors to screen small compound libraries to discover potential inhibitors of CA IX. Molecular docking experiments discovered that four compounds ZINC613262012, ZINC427910039, ZINC616453231, and DB00482 exhibited a strong binding affinity towards CA IX, mimicking the interaction pattern similar to native inhibitors. Molecular dynamics simulations and an MM-PBSA analysis revealed ZINC613262012, ZINC427910039, and DB00482 as the most potential and stable inhibitors with the binding free energies −10.92, −18.77, and −12.29 kcal/mol, respectively. In addition, DFT-based analyses supported their favorable electronic properties, further validating their potential as CA IX inhibitors. These three hits demonstrated a greater stability and compactness relative to the known inhibitors, suggesting these might be used CA IX inhibitors to treat tumors.
Share and Cite
MDPI and ACS Style
Almansour, N.M.
Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy. Int. J. Mol. Sci. 2025, 26, 8465.
https://doi.org/10.3390/ijms26178465
AMA Style
Almansour NM.
Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy. International Journal of Molecular Sciences. 2025; 26(17):8465.
https://doi.org/10.3390/ijms26178465
Chicago/Turabian Style
Almansour, Nahlah Makki.
2025. "Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy" International Journal of Molecular Sciences 26, no. 17: 8465.
https://doi.org/10.3390/ijms26178465
APA Style
Almansour, N. M.
(2025). Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy. International Journal of Molecular Sciences, 26(17), 8465.
https://doi.org/10.3390/ijms26178465
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details
here.
Article Metrics
Article Access Statistics
For more information on the journal statistics, click
here.
Multiple requests from the same IP address are counted as one view.