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Discovery of Potential Fgfr3 Inhibitors Via Qsar, Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies Against Bladder Cancer Publisher Pubmed



Ganji M1 ; Bakhshi S2 ; Shoari A3 ; Ahangari Cohan R4
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  2. 2. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  4. 4. Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, No. 69, Pasteur Ave, Tehran, 1316543551, Iran

Source: Journal of Translational Medicine Published:2023


Abstract

Background: Fibroblast growth factor receptor 3 is known as a favorable aim in vast range of cancers, particularly in bladder cancer treatment. Pharmacophore and QSAR modeling approaches are broadly utilized for developing novel compounds for the determination of inhibitory activity versus the biological target. In this study, these methods employed to identify FGFR3 potential inhibitors. Methods: To find the potential compounds for bladder cancer targeting, ZINC and NCI databases were screened. Pharmacophore and QSAR modeling of FGFR3 inhibitors were utilized for dataset screening. Then, with regard to several factors such as Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties and Lipinski’s Rule of Five, the recognized compounds were filtered. In further step, utilizing the flexible docking technique, the obtained compounds interactions with FGFR3 were analyzed. Results: The best five compounds, namely ZINC09045651, ZINC08433190, ZINC00702764, ZINC00710252 and ZINC00668789 were selected for Molecular Dynamics (MD) studies. Off-targeting of screened compounds was also investigated through CDD search and molecular docking. MD outcomes confirmed docking investigations and revealed that five selected compounds could make steady interactions with the FGFR3 and might have effective inhibitory potencies on FGFR3. Conclusion: These compounds can be considered as candidates for bladder cancer therapy with improved therapeutic properties and less adverse effects. © 2023, The Author(s).
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