Determination of the CYP2B6 Component of 7-Ethoxy-4-Trifluoromethylcoumarin O-Deethylation Activity in Human Liver Microsomes
Bibliographic record
Abstract
CYP2B6 protein has been isolated and purified from human liver (, ). In a panel of 60 individual human liver microsome samples, this P450 accounts for <l% of total P450 content in human liver (). However, a large mtermdlvldual variability has been reported for the hepatic levels of CYP2B6 mRNA () and protein (, , ). Experiments with primary cultures of human hepatocytes have shown that CYP2B6 is inducible by treatment of the cells with phenobarbital (), dexamethasone (, ), or rifampm (rifampicm) ($6). By contrast, the level of this P450 in hepatocyte cultures does not appear to be altered by other P450 mducers such as /3-naphthoflavone (), 2,3,7,8-tetrachlorodibenzo-p-dloxm () or pregnenolone 16a-carbonitnle (). Several substrates have been ldentlfied for cDNA-expressed CYP2B6, including I-l-ethoxycoumarin (, , ), benzo[a]pyrene (), phenanthrene (), and methoxychlor (). However, little is known regardmg the role of this P450 in drug metabolism, although cDNA-expressed CYP2B6 is an active catalyst of lidocaine N-deethylatlon () and human hver microsomal CYP2B6 appears to be a high-Km catalyst of cyclophosphamlde 4-hydroxylation (). Detailed mvestlgations of hepatic mlcrosomal CYP2B6 have been limited because: 1 Many of the heterologous anti-CYP2B antibody preparations are not useful owing to their slgmficant cross-reactivity with other human P450 enzymes; 2 A CYP2B6-specific chemical inhibitor has yet to be found; and 3 A dlagnostlc catalytic activity for human hepatlc mlcrosomal CYP2B6 has not been identified.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".