CYTOCHROME P450 2C8 (CYP2C8)-MEDIATED HYDROXYLATION OF AN ENDOTHELIN ET A RECEPTOR ANTAGONIST IN HUMAN LIVER MICROSOMES
Drug Metabolism and Disposition, ISSN: 0090-9556, Vol: 32, Issue: 5, Page: 473-478
2004
- 7Citations
- 3Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Article Description
In vitro studies were performed to identify the human cytochrome P450 enzyme(s) involved in the hydroxylation (isopropyl moiety) of a previously reported endothelin ET A receptor antagonist, compound A [(+)-(5 S,6 R,7 R )-2-isopropylamino-7-{4-methoxy-2-[(2 R )-3-methoxy-2-methylpropyl]}-5-(3,4-methylenedioxyphenyl)cyclopenteno(1,2- b ) pyridine 6-carboxylic acid]. Several lines of evidence indicated that the reaction was mainly catalyzed by CYP2C8. Of the 10 recombinant cytochrome P450 isoforms tested, only CYP2C8 exhibited hydroxylase activity. In agreement, inhibitory antibodies selective for CYP2C8 attenuated (>95%) the hydroxylase activity in human liver microsomes, whereas antibodies and chemical inhibitors selective for other cytochrome P450 isoforms had a minor or no effect on the reaction. In addition, the formation of the hydroxy metabolite correlated well with CYP2C8-selective paclitaxel 6α-hydroxylation ( r 2 ∼0.92; p < 0.0001) and amodiaquine N -de-ethylation ( r 2 ∼0.91; p < 0.0001) in a bank of human liver microsomes ( n = 15 organ donors). Finally, compound A hydroxylase activity conformed to Michaelis-Menten kinetics, and the K m (Michaelis constant) in human liver microsomes was similar to that of CYP2C8 (∼10 μM). It is concluded that the hydroxylation of compound A is mainly catalyzed by CYP2C8, and thus the reaction can possibly serve as an alternative marker assay for CYP2C8 in human liver microsomes.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0090955624029003; http://dx.doi.org/10.1124/dmd.32.5.473; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=2042546727&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/15100167; https://linkinghub.elsevier.com/retrieve/pii/S0090955624029003; https://dx.doi.org/10.1124/dmd.32.5.473; https://dmd.aspetjournals.org/content/32/5/473
Elsevier BV
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know