Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer
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 t...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-03955-5 |
| _version_ | 1811165790606458880 |
|---|---|
| author | Mahmoud Ganji Shohreh Bakhshi Alireza Shoari Reza Ahangari Cohan |
| author_facet | Mahmoud Ganji Shohreh Bakhshi Alireza Shoari Reza Ahangari Cohan |
| author_sort | Mahmoud Ganji |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T15:42:18Z |
| format | Article |
| id | doaj.art-aa62e227eb9c4bee82cb31349c12f3d0 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T15:42:18Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-aa62e227eb9c4bee82cb31349c12f3d02023-02-12T12:20:58ZengBMCJournal of Translational Medicine1479-58762023-02-0121112210.1186/s12967-023-03955-5Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancerMahmoud Ganji0Shohreh Bakhshi1Alireza Shoari2Reza Ahangari Cohan3Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares UniversityFaculty of Pharmacy, Tehran University of Medical SciencesBiotechnology Research Center, Pasteur Institute of IranDepartment of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of IranAbstract 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.https://doi.org/10.1186/s12967-023-03955-5Bladder cancerDrug discoveryPharmacophoreQSARDockingMolecular dynamics |
| spellingShingle | Mahmoud Ganji Shohreh Bakhshi Alireza Shoari Reza Ahangari Cohan Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer Journal of Translational Medicine Bladder cancer Drug discovery Pharmacophore QSAR Docking Molecular dynamics |
| title | Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer |
| title_full | Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer |
| title_fullStr | Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer |
| title_full_unstemmed | Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer |
| title_short | Discovery of potential FGFR3 inhibitors via QSAR, pharmacophore modeling, virtual screening and molecular docking studies against bladder cancer |
| title_sort | discovery of potential fgfr3 inhibitors via qsar pharmacophore modeling virtual screening and molecular docking studies against bladder cancer |
| topic | Bladder cancer Drug discovery Pharmacophore QSAR Docking Molecular dynamics |
| url | https://doi.org/10.1186/s12967-023-03955-5 |
| work_keys_str_mv | AT mahmoudganji discoveryofpotentialfgfr3inhibitorsviaqsarpharmacophoremodelingvirtualscreeningandmoleculardockingstudiesagainstbladdercancer AT shohrehbakhshi discoveryofpotentialfgfr3inhibitorsviaqsarpharmacophoremodelingvirtualscreeningandmoleculardockingstudiesagainstbladdercancer AT alirezashoari discoveryofpotentialfgfr3inhibitorsviaqsarpharmacophoremodelingvirtualscreeningandmoleculardockingstudiesagainstbladdercancer AT rezaahangaricohan discoveryofpotentialfgfr3inhibitorsviaqsarpharmacophoremodelingvirtualscreeningandmoleculardockingstudiesagainstbladdercancer |