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Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4

Cytochrome P450 2B6 (CYP2B6) is a human enzyme important in chemical detoxification, steroid and fatty acid metabolism that is primarily hepatic. Therefore, induction or inhibition of CYP2B6 may perturb endo- and xenobiotic metabolism and cause adverse reactions. Recent research indicates that mice...

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Autores principales: Olack, Emily M., Heintz, Melissa M., Baldwin, William S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8914530/
https://www.ncbi.nlm.nih.gov/pubmed/35282180
http://dx.doi.org/10.1016/j.dib.2022.108013
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author Olack, Emily M.
Heintz, Melissa M.
Baldwin, William S.
author_facet Olack, Emily M.
Heintz, Melissa M.
Baldwin, William S.
author_sort Olack, Emily M.
collection PubMed
description Cytochrome P450 2B6 (CYP2B6) is a human enzyme important in chemical detoxification, steroid and fatty acid metabolism that is primarily hepatic. Therefore, induction or inhibition of CYP2B6 may perturb endo- and xenobiotic metabolism and cause adverse reactions. Recent research indicates that mice lacking Cyp2b enzymes are obese with liver steatosis [1] (Heintz et al., J Nutr Biochem, 70:125–137, 2019). Current work is underway to determine the role of CYP2B6 in obesity and fatty acid metabolism, and CYP2B6 fluorescent inhibition assays were used to determine the IC50s of multiple industrial chemicals, pesticides, bile acids, steroids, and fatty acids. In many cases, inhibition of CYP3A4 was also performed in comparison because CYP3A4 is the most abundant hepatic detoxification CYP and therefore by abundance alone may also play a key role in the chemical's metabolism. Further, using the ratio of comparative potency of these compounds for CYP2B6 and CYP3A4, specificity can be estimated for these CYP2B6 inhibitors. These results indicate strong preferential inhibition (greater than 10-fold) of CYP2B6 and include lithocholic acid, arachidonic acid, atrazine, chlorpyrifos, endosulfan, parathion, and nonylphenol. Estradiol was a strong preferential inhibitor of CYP3A4. Other screened CYP2B6 inhibitors include triclosan, ticlopidine, jet fuel, docosahexaenoic acid, linoleic acid, linolenic acid, oleic acid, lithocholic acid, butylate, hexachlorocyclohexane, vinclozolin, pentachlorophenol, metalachlor, butylate, diazinon, avermectin, tribufos, ticlopidine, and bisphenol A. Documentation of xenobiotic and endobiotic inhibition by these CYPs is necessary for proper modeling of the effects of diet, chemical exposure or even mixtures on drug metabolism and potential adverse reactions.
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spelling pubmed-89145302022-03-12 Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4 Olack, Emily M. Heintz, Melissa M. Baldwin, William S. Data Brief Data Article Cytochrome P450 2B6 (CYP2B6) is a human enzyme important in chemical detoxification, steroid and fatty acid metabolism that is primarily hepatic. Therefore, induction or inhibition of CYP2B6 may perturb endo- and xenobiotic metabolism and cause adverse reactions. Recent research indicates that mice lacking Cyp2b enzymes are obese with liver steatosis [1] (Heintz et al., J Nutr Biochem, 70:125–137, 2019). Current work is underway to determine the role of CYP2B6 in obesity and fatty acid metabolism, and CYP2B6 fluorescent inhibition assays were used to determine the IC50s of multiple industrial chemicals, pesticides, bile acids, steroids, and fatty acids. In many cases, inhibition of CYP3A4 was also performed in comparison because CYP3A4 is the most abundant hepatic detoxification CYP and therefore by abundance alone may also play a key role in the chemical's metabolism. Further, using the ratio of comparative potency of these compounds for CYP2B6 and CYP3A4, specificity can be estimated for these CYP2B6 inhibitors. These results indicate strong preferential inhibition (greater than 10-fold) of CYP2B6 and include lithocholic acid, arachidonic acid, atrazine, chlorpyrifos, endosulfan, parathion, and nonylphenol. Estradiol was a strong preferential inhibitor of CYP3A4. Other screened CYP2B6 inhibitors include triclosan, ticlopidine, jet fuel, docosahexaenoic acid, linoleic acid, linolenic acid, oleic acid, lithocholic acid, butylate, hexachlorocyclohexane, vinclozolin, pentachlorophenol, metalachlor, butylate, diazinon, avermectin, tribufos, ticlopidine, and bisphenol A. Documentation of xenobiotic and endobiotic inhibition by these CYPs is necessary for proper modeling of the effects of diet, chemical exposure or even mixtures on drug metabolism and potential adverse reactions. Elsevier 2022-03-04 /pmc/articles/PMC8914530/ /pubmed/35282180 http://dx.doi.org/10.1016/j.dib.2022.108013 Text en © 2022 The Author(s). Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Data Article
Olack, Emily M.
Heintz, Melissa M.
Baldwin, William S.
Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4
title Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4
title_full Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4
title_fullStr Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4
title_full_unstemmed Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4
title_short Dataset of endo- and xenobiotic inhibition of CYP2B6: Comparison to CYP3A4
title_sort dataset of endo- and xenobiotic inhibition of cyp2b6: comparison to cyp3a4
topic Data Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8914530/
https://www.ncbi.nlm.nih.gov/pubmed/35282180
http://dx.doi.org/10.1016/j.dib.2022.108013
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