Next Article in Journal
Methods and Guidelines for Metabolism Studies: Applications to Cancer Research
Previous Article in Journal
Integrated Approach for Biochemical and Functional Characterization of Six Clinical Variants of Glucose-6-Phosphate Dehydrogenase
Previous Article in Special Issue
Molecular Mechanisms of Phytochemicals from Chaga Mushroom (Inonotus obliquus) Against Colorectal Cancer: Insights from Network Pharmacology, Molecular Docking, and Bioinformatics
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy

by
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.
Keywords: Carbonic Anhydrase IX; inhibitors; pharmacophore model; molecular docking Carbonic Anhydrase IX; inhibitors; pharmacophore model; molecular docking

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

Back to TopTop