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The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study
Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural c...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144134/ https://www.ncbi.nlm.nih.gov/pubmed/35621970 http://dx.doi.org/10.3390/md20050319 |
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author | Luo, Lianxiang Wang, Qu Liao, Yinglin |
author_facet | Luo, Lianxiang Wang, Qu Liao, Yinglin |
author_sort | Luo, Lianxiang |
collection | PubMed |
description | Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6. |
format | Online Article Text |
id | pubmed-9144134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91441342022-05-29 The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study Luo, Lianxiang Wang, Qu Liao, Yinglin Mar Drugs Article Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6. MDPI 2022-05-12 /pmc/articles/PMC9144134/ /pubmed/35621970 http://dx.doi.org/10.3390/md20050319 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Luo, Lianxiang Wang, Qu Liao, Yinglin The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study |
title | The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study |
title_full | The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study |
title_fullStr | The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study |
title_full_unstemmed | The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study |
title_short | The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study |
title_sort | inhibitors of cdk4/6 from a library of marine compound database: a pharmacophore, admet, molecular docking and molecular dynamics study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144134/ https://www.ncbi.nlm.nih.gov/pubmed/35621970 http://dx.doi.org/10.3390/md20050319 |
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