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Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450

Human cytochrome P450 enzymes (CYPs) are heme-containing monooxygenases. This superfamily of drug-metabolizing enzymes is responsible for the metabolism of most drugs and other xenobiotics. The inhibition of CYPs may lead to drug–drug interactions and impair the biotransformation of drugs. CYP induc...

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Autores principales: Rudik, Anastassia, Dmitriev, Alexander, Lagunin, Alexey, Filimonov, Dmitry, Poroikov, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503090/
https://www.ncbi.nlm.nih.gov/pubmed/36144612
http://dx.doi.org/10.3390/molecules27185875
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author Rudik, Anastassia
Dmitriev, Alexander
Lagunin, Alexey
Filimonov, Dmitry
Poroikov, Vladimir
author_facet Rudik, Anastassia
Dmitriev, Alexander
Lagunin, Alexey
Filimonov, Dmitry
Poroikov, Vladimir
author_sort Rudik, Anastassia
collection PubMed
description Human cytochrome P450 enzymes (CYPs) are heme-containing monooxygenases. This superfamily of drug-metabolizing enzymes is responsible for the metabolism of most drugs and other xenobiotics. The inhibition of CYPs may lead to drug–drug interactions and impair the biotransformation of drugs. CYP inducers may decrease the bioavailability and increase the clearance of drugs. Based on the freely available databases ChEMBL and PubChem, we have collected over 70,000 records containing the structures of inhibitors and inducers together with the IC50 values for the inhibitors of the five major human CYPs: 1A2, 3A4, 2D6, 2C9, and 2C19. Based on the collected data, we developed (Q)SAR models for predicting inhibitors and inducers of these CYPs using GUSAR and PASS software. The developed (Q)SAR models could be applied for assessment of the interaction of novel drug-like substances with the major human CYPs. The created (Q)SAR models demonstrated reasonable accuracy of prediction. They have been implemented in the web application P450-Analyzer that is freely available via the Internet.
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spelling pubmed-95030902022-09-24 Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450 Rudik, Anastassia Dmitriev, Alexander Lagunin, Alexey Filimonov, Dmitry Poroikov, Vladimir Molecules Article Human cytochrome P450 enzymes (CYPs) are heme-containing monooxygenases. This superfamily of drug-metabolizing enzymes is responsible for the metabolism of most drugs and other xenobiotics. The inhibition of CYPs may lead to drug–drug interactions and impair the biotransformation of drugs. CYP inducers may decrease the bioavailability and increase the clearance of drugs. Based on the freely available databases ChEMBL and PubChem, we have collected over 70,000 records containing the structures of inhibitors and inducers together with the IC50 values for the inhibitors of the five major human CYPs: 1A2, 3A4, 2D6, 2C9, and 2C19. Based on the collected data, we developed (Q)SAR models for predicting inhibitors and inducers of these CYPs using GUSAR and PASS software. The developed (Q)SAR models could be applied for assessment of the interaction of novel drug-like substances with the major human CYPs. The created (Q)SAR models demonstrated reasonable accuracy of prediction. They have been implemented in the web application P450-Analyzer that is freely available via the Internet. MDPI 2022-09-10 /pmc/articles/PMC9503090/ /pubmed/36144612 http://dx.doi.org/10.3390/molecules27185875 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
Rudik, Anastassia
Dmitriev, Alexander
Lagunin, Alexey
Filimonov, Dmitry
Poroikov, Vladimir
Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450
title Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450
title_full Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450
title_fullStr Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450
title_full_unstemmed Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450
title_short Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450
title_sort computational prediction of inhibitors and inducers of the major isoforms of cytochrome p450
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503090/
https://www.ncbi.nlm.nih.gov/pubmed/36144612
http://dx.doi.org/10.3390/molecules27185875
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