Mechanism-based inhibition of CYP2B6 in human liver microsomes by thienopyridine antiplatelet agents ticlopidine and clopidogrel and the thiolactone metabolites of those two agents plus that of prasugrel were investigated by determining the time- and concentration-dependent inhibition of the activity of bupropion hydroxylase as the typical CYP2B6 activity. Storage: -80. In a panel of 11 HLMs, 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz formation rates from efavirenz (10 micro M) correlated significantly with the activity of CYP2B6 and CYP3A . N,N',N"-Triethylenethiophosphoramide (thioTEPA; 50 micro M) inhibited the formation rates of 8-hydroxyefavirenz and 8, 14-dihydroxyefavirenz from efavirenz (10 micro M) by > or = 60% in HLMs) and CYP2B6, with Ki values < 4 micro M. In conclusion, CYP2B6 is the principal catalyst of efavirenz sequential hydroxylation. CYP2B6 represents approximately 6% of the hepatic cytochrome P450 pool and demonstrates more than 100-fold interindividual variability in the activity. In addition, genetic polymorphism in CYP2B6 was shown to result in decreased enzyme activity.
Efavirenz may be a valuable phenotyping tool to study the role of CYP2B6 in human drug metabolism.
Even more, Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The structure supports prior P450 2B6 homology models based on other mammalian cytochromes P450 and is consistent with the limited site-directed mutagenesis studies on 2B6 and extensive studies on P450 2B4 and 2B1.
Stability:2 years
More about: Cytochrome P450 2B6 (human) Yeast Reductase Sale
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