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Chemical Compound Review:

PubChem13296 7-ethoxy-4- (trifluoromethyl)chromen-2- one

Synonyms: Etfc cpd, ACMC-1C8TY, CBMicro_044809, AG-D-36502, T2803_SIGMA, ...

Domanski, T.L. et al., Spatzenegger, M. et al., Penman, B.W. et al., Jinno, H. et al., Scott, E.E. et al., et al.

Scott, Spatzenegger, Halpert, Domanski, Schultz, Roussel, Stevens, Halpert,

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High impact information on Etfc cpd

7-Ethoxy-4-trifluoromethylcoumarin (7-EFC) was examined as a substrate for cytochrome P450 (P450) in microsomes from human livers and expressed in B-lymphoblastoid cells [1].
Use of three-dimensional models of CYP2B6 and CYP2E1 based on the crystal structure of CYP2C5 suggested that deethylation of 7-ethoxy-4-trifluoromethylcoumarin by CYP2E1 is impeded by van der Waals overlaps with the side chain of Phe-477 [2].
Mutants F107I and L363V exhibited decreased RP 73401 hydroxylation but retained most of the wild-type level of 2B6 7-ethoxy-4-trifluoromethylcoumarin O-deethylase activity [3].
The 2B6 mutants were expressed in Spodoptera frugiperda cells and characterized using the 2B6-specific substrate RP 73401 [3-cyclopentyloxy-N-(3,5-dichloro-4-pyridyl)-4-methoxybenzamide], the 2B1-selective substrate androstenedione, and the common substrate 7-ethoxy-4-trifluoromethylcoumarin [3].
Wild-type (CYP2B6.1) and all of the known variants of CYP2B6 (CYP2B6.2, CYP2B6.3, CYP2B6.4, CYP2B6.5, CYP2B6.6, and CYP2B6.7) were transiently expressed in COS-1 cells, and their 7-ethoxy-4-trifluoromethylcoumarin O-deethylation activities were determined [4].

Biological context of Etfc cpd

Benzyloxyresorufin and 7-ethoxy-4-trifluoromethylcoumarin, the two lowest K(m) substrates in the training set, were then docked in the active site of CYP2B6 [5].

Anatomical context of Etfc cpd

The O-deethylation of 7-ethoxy-4-trifluoromethylcoumarin (EFC) by liver microsomes has been assessed as a method for monitoring the activity of cytochrome P450 [6].

Associations of Etfc cpd with other chemical compounds

Microsomes prepared from CYP1A1 cDNA expressing cells exhibit high, constitutive levels of 7-ethoxyresorufin deethylase (EROD), 7-ethoxycoumarin deethylase (ECD), 7-ethoxy-4-trifluoromethylcoumarin deethylase (EFCD), benzo[a]-pyrene hydroxylase (BPH) activities and spectrally quantifiable cytochrome P450 [7].
One of the most intriguing findings was that substitution of CYP2E1 Phe-477 with valine from CYP2B6 resulted in significant 7-ethoxy-4-trifluoromethylcoumarin deethylation [2].
All truncated proteins, including human 2B6, were active with 7-ethoxy-4-trifluoromethylcoumarin, and truncated 2B1 was shown to retain the native regio- and stereospecificity of testosterone hydroxylation [8].

Analytical, diagnostic and therapeutic context of Etfc cpd

An HPLC method for analysis of deethylation of 7-ethoxy-4-trifluoromethylcoumarin (ETFMC), a substrate of various enzymes of the cytochrome P450 superfamily, was developed [9].

References

Examination of purported probes of human CYP2B6. Ekins, S., VandenBranden, M., Ring, B.J., Wrighton, S.A. Pharmacogenetics (1997) [Pubmed]
Analysis of differential substrate selectivities of CYP2B6 and CYP2E1 by site-directed mutagenesis and molecular modeling. Spatzenegger, M., Liu, H., Wang, Q., Debarber, A., Koop, D.R., Halpert, J.R. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
Structure-function analysis of human cytochrome P-450 2B6 using a novel substrate, site-directed mutagenesis, and molecular modeling. Domanski, T.L., Schultz, K.M., Roussel, F., Stevens, J.C., Halpert, J.R. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
Functional characterization of cytochrome P450 2B6 allelic variants. Jinno, H., Tanaka-Kagawa, T., Ohno, A., Makino, Y., Matsushima, E., Hanioka, N., Ando, M. Drug Metab. Dispos. (2003) [Pubmed]
Combined three-dimensional quantitative structure-activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling. Wang, Q., Halpert, J.R. Drug Metab. Dispos. (2002) [Pubmed]
A highly sensitive tool for the assay of cytochrome P450 enzyme activity in rat, dog and man. Direct fluorescence monitoring of the deethylation of 7-ethoxy-4-trifluoromethylcoumarin. Buters, J.T., Schiller, C.D., Chou, R.C. Biochem. Pharmacol. (1993) [Pubmed]
Development of a human lymphoblastoid cell line constitutively expressing human CYP1A1 cDNA: substrate specificity with model substrates and promutagens. Penman, B.W., Chen, L., Gelboin, H.V., Gonzalez, F.J., Crespi, C.L. Carcinogenesis (1994) [Pubmed]
A truncation of 2B subfamily cytochromes P450 yields increased expression levels, increased solubility, and decreased aggregation while retaining function. Scott, E.E., Spatzenegger, M., Halpert, J.R. Arch. Biochem. Biophys. (2001) [Pubmed]
High-performance liquid chromatographic method for measurement of cytochrome P450-mediated metabolism of 7-ethoxy-4-trifluoromethylcoumarin. Morse, M.A., Lu, J. J. Chromatogr. B Biomed. Sci. Appl. (1998) [Pubmed]

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