A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ
Fragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach in the drug discovery process, leading to several drug candidates under investigation in clinical trials and some approved drugs. Among these successful applications of the FBDD approach, kinases represent a cl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9741 |
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| author | Giovanni Bolcato Eleonora Cescon Matteo Pavan Maicol Bissaro Davide Bassani Stephanie Federico Giampiero Spalluto Mattia Sturlese Stefano Moro |
| author_facet | Giovanni Bolcato Eleonora Cescon Matteo Pavan Maicol Bissaro Davide Bassani Stephanie Federico Giampiero Spalluto Mattia Sturlese Stefano Moro |
| author_sort | Giovanni Bolcato |
| collection | DOAJ |
| description | Fragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach in the drug discovery process, leading to several drug candidates under investigation in clinical trials and some approved drugs. Among these successful applications of the FBDD approach, kinases represent a class of targets where this strategy has demonstrated its real potential with the approved kinase inhibitor Vemurafenib. In the Kinase family, protein kinase CK1 isoform δ (CK1δ) has become a promising target in the treatment of different neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the present work, we set up and applied a computational workflow for the identification of putative fragment binders in large virtual databases. To validate the method, the selected compounds were tested in vitro to assess the CK1δ inhibition. |
| first_indexed | 2024-03-10T07:36:37Z |
| format | Article |
| id | doaj.art-4a85a58ae9a34b8f8086f602bb1243d9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:36:37Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4a85a58ae9a34b8f8086f602bb1243d92023-11-22T13:26:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218974110.3390/ijms22189741A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δGiovanni Bolcato0Eleonora Cescon1Matteo Pavan2Maicol Bissaro3Davide Bassani4Stephanie Federico5Giampiero Spalluto6Mattia Sturlese7Stefano Moro8Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgeri 1, 34127 Trieste, ItalyMolecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, ItalyMolecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, ItalyMolecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgeri 1, 34127 Trieste, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgeri 1, 34127 Trieste, ItalyMolecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, ItalyMolecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, ItalyFragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach in the drug discovery process, leading to several drug candidates under investigation in clinical trials and some approved drugs. Among these successful applications of the FBDD approach, kinases represent a class of targets where this strategy has demonstrated its real potential with the approved kinase inhibitor Vemurafenib. In the Kinase family, protein kinase CK1 isoform δ (CK1δ) has become a promising target in the treatment of different neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the present work, we set up and applied a computational workflow for the identification of putative fragment binders in large virtual databases. To validate the method, the selected compounds were tested in vitro to assess the CK1δ inhibition.https://www.mdpi.com/1422-0067/22/18/9741fragment-based drug discoverymolecular dockingmolecular dynamicssupervised molecular dynamicsprotein kinase CK1δ |
| spellingShingle | Giovanni Bolcato Eleonora Cescon Matteo Pavan Maicol Bissaro Davide Bassani Stephanie Federico Giampiero Spalluto Mattia Sturlese Stefano Moro A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ International Journal of Molecular Sciences fragment-based drug discovery molecular docking molecular dynamics supervised molecular dynamics protein kinase CK1δ |
| title | A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ |
| title_full | A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ |
| title_fullStr | A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ |
| title_full_unstemmed | A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ |
| title_short | A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ |
| title_sort | computational workflow for the identification of novel fragments acting as inhibitors of the activity of protein kinase ck1δ |
| topic | fragment-based drug discovery molecular docking molecular dynamics supervised molecular dynamics protein kinase CK1δ |
| url | https://www.mdpi.com/1422-0067/22/18/9741 |
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