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

Rudik, Anastassia; Dmitriev, Alexander; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir

doi:10.3390/molecules27185875

Open AccessArticle

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

by

Anastassia Rudik

¹,

Alexander Dmitriev

¹

,

Alexey Lagunin

^1,2

,

Dmitry Filimonov

¹ and

Vladimir Poroikov

^1,*

¹

Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Str. 10, Bldg.8, 119121 Moscow, Russia

²

Department of Bioinformatics, Pirogov Russian National Research Medical University, Ostrovityanova Str. 1, 117513 Moscow, Russia

^*

Author to whom correspondence should be addressed.

Molecules 2022, 27(18), 5875; https://doi.org/10.3390/molecules27185875

Submission received: 17 August 2022 / Revised: 6 September 2022 / Accepted: 8 September 2022 / Published: 10 September 2022

(This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research 3.0)

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Abstract

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.

Keywords: CYP; inhibitors; inducers; (Q)SAR models; PASS; GUSAR; drug-like compounds; metabolism; in silico prediction; P450 isoforms; 1A2; 3A4; 2D6; 2C9; 2C19

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MDPI and ACS Style

Rudik, A.; Dmitriev, A.; Lagunin, A.; Filimonov, D.; Poroikov, V. Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450. Molecules 2022, 27, 5875. https://doi.org/10.3390/molecules27185875

AMA Style

Rudik A, Dmitriev A, Lagunin A, Filimonov D, Poroikov V. Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450. Molecules. 2022; 27(18):5875. https://doi.org/10.3390/molecules27185875

Chicago/Turabian Style

Rudik, Anastassia, Alexander Dmitriev, Alexey Lagunin, Dmitry Filimonov, and Vladimir Poroikov. 2022. "Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450" Molecules 27, no. 18: 5875. https://doi.org/10.3390/molecules27185875

APA Style

Rudik, A., Dmitriev, A., Lagunin, A., Filimonov, D., & Poroikov, V. (2022). Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450. Molecules, 27(18), 5875. https://doi.org/10.3390/molecules27185875

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

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