The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

SureCN104497     7-ethoxyphenoxazin-3-one

Synonyms: AG-J-47873, CHEMBL1080002, CHEBI:34480, AC1L1FLW, CTK5A6532, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of C13630

  • ICZ has a Kd of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC50 of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells [1].
  • In concordance, total CYP1A1 activity, as measured by the ethoxyresorufin O-deethylase assay, was detected in mitochondrial, nuclear, and microsomal fractions of ovarian cancer cells but was notably absent in all subcellular fractions of HOSE cells [2].
  • Finally, P450 1A2 and 1A2-supported ethoxyresorufin O-deethylase activity were significantly reduced in hepatic microsomes from patients with both types of advanced liver disease [3].
  • The expressed protein from E. coli membranes had a CO-binding spectrum typical of P450s, and it catalyzed the O-dealkylation of the CYP1A prototype substrates ethoxyresorufin and methoxyresorufin [4].
  • We determined if individual PAHs and other procarcinogens affect the activities of human P450s 1A1, 1A2, and 1B1 by measuring 7-ethoxyresorufin O-deethylation (EROD) activity and metabolic activation of PAH dihydrodiols and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline (MeIQ) to genotoxic metabolites in a Salmonella typhimurium NM2009 system [5].

High impact information on C13630

  • The induction of cytochrome P450 1A1 transcripts by WY-14643 was associated with a marked increase of ethoxyresorufin O -deethylase activity (10-fold at 200 mumol/L) [6].
  • P450-dependent enzymatic activity was assessed by deethylation of ethoxyresorufin [7].
  • Of the mutations made, the substitution of Trp-676 with alanine (W676A) resulted in a functional NADH-dependent enzyme, which catalyzed the reduction of cytochrome c and ferricyanide as well as facilitated the metabolism of 7-ethoxyresorufin by CYP1A2 [8].
  • Clotrimazole (0.7 microM) and 7-ethoxyresorufin (1 microM), both considered to be specific inhibitors of the cytochrome P-450 monooxygenase enzymes, inhibited the vasodilator effect, suggesting that AA-induced renal vasodilation is mediated by one or more cytochrome P-450-derived AA metabolites [9].
  • Curcumin increased both expression (reverse transcription-PCR analyses) and function (high-performance liquid chromatography determination of ethoxyresorufin metabolism) of cytochrome P-450 (CYP) 1A1 and/or CYP1B1 [10].

Chemical compound and disease context of C13630


Biological context of C13630


Anatomical context of C13630

  • CYP1A1 messenger RNA (mRNA) and ethoxyresorufin activity were present constitutively in the duodenum of each volunteer [7].
  • In hepatic microsomes from methylcholanthrene-treated chicks and rats, MeIQ was a competitive inhibitor of both ethoxyresorufin deethylase activity, a reaction catalyzed mainly by rodent cytochrome P450 IA1, and uroporphyrinogen oxidation, a reaction catalyzed by rodent P450 IA2 [21].
  • The induction of ethoxyresorufin O-deethylase in the T47-D cells was the most sensitive aryl hydrocarbon (Ah) receptor-mediated response in both cell lines and this enzyme activity was more inducible than aryl hydrocarbon hydroxylase [22].
  • Ethoxyresorufin O-deethylase activity was low to nondetectable in noninduced, mitogen-activated cells, but it was readily detected in 3-methylcholanthrene, mitogen-activated lymphocytes [23].
  • The basal activity of 7-ethoxyresorufin O-deethylation of the mucosa of the ethmoturbinates of the rat was comparable to the corresponding activity of the liver [24].

Associations of C13630 with other chemical compounds

  • Inhibition by OPZ of AFB1 metabolism by reducing CYP1A2 and CYP3A4 was also demonstrated by decreased activity of their monooxygenase activities toward ethoxyresorufin and nifedipine, respectively [25].
  • Anti-P-450 reductase immunoglobulin G inhibited reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase activity in prostatic microsomes, and anti-P-450 BNF-B2 but not anti-P-450 PB-B2 immunoglobulin G inhibited the BNF-induced prostatic microsomal 7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase activities [26].
  • The TA1538/ARO strain was proven to express the enzymes, as indicated by high activities of 7-ethoxyresorufin O-deethylase and isoniazid N-acetylase [27].
  • AHH, 7-ethoxycoumarin O-deethylase (ECOD), and 7-ethoxyresorufin O-deethylase (EROD) have been used most frequently as substrates to characterize intestinal P450s [28].
  • Serial measurements of albumin secretion, urea synthesis, deethylation of ethoxyresorufin (CYT P450 activity), and responsiveness to stimulation with interleukin-6 (IL-6) were performed [29].

Gene context of C13630


Analytical, diagnostic and therapeutic context of C13630

  • Since in hepatic and pulmonary tissue of model animal systems ethoxyresorufin is a specific substrate for cytochrome P-448-associated monooxygenases, the use of this chemical could proffer an assay that specifically measures human cytochrome P-448-associated activity [23].
  • O-Deethylation of 7-ethoxyresorufin was neither sex differentiated nor affected by castration [35].
  • Here, we report on the localization of CYP1A1 in the cytosol of kidney and brain, as revealed by immunoblotting with anti-CYP1A1 antibodies and by 7-ethoxyresorufin deethylation (EROD) [36].
  • Western blotting together with assays for 7-ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase established that I3C preferentially induced cytochrome P4501A1 over 1A2, consistent with the altered profile of urinary metabolites [37].
  • Induction of cytochrome P450 1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity in mammalian cell culture (EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxinlike compounds [38].


  1. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Bjeldanes, L.F., Kim, J.Y., Grose, K.R., Bartholomew, J.C., Bradfield, C.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  2. Overexpression of cytochrome P450 1A1 and its novel spliced variant in ovarian cancer cells: alternative subcellular enzyme compartmentation may contribute to carcinogenesis. Leung, Y.K., Lau, K.M., Mobley, J., Jiang, Z., Ho, S.M. Cancer Res. (2005) [Pubmed]
  3. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. George, J., Murray, M., Byth, K., Farrell, G.C. Hepatology (1995) [Pubmed]
  4. Molecular cloning and expression of a novel cytochrome p450 from turkey liver with aflatoxin b1 oxidizing activity. Yip, S.S., Coulombe, R.A. Chem. Res. Toxicol. (2006) [Pubmed]
  5. Inhibition of human cytochrome P450 1A1-, 1A2-, and 1B1-mediated activation of procarcinogens to genotoxic metabolites by polycyclic aromatic hydrocarbons. Shimada, T., Guengerich, F.P. Chem. Res. Toxicol. (2006) [Pubmed]
  6. Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites. Sérée, E., Villard, P.H., Pascussi, J.M., Pineau, T., Maurel, P., Nguyen, Q.B., Fallone, F., Martin, P.M., Champion, S., Lacarelle, B., Savouret, J.F., Barra, Y. Gastroenterology (2004) [Pubmed]
  7. Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract. McDonnell, W.M., Scheiman, J.M., Traber, P.G. Gastroenterology (1992) [Pubmed]
  8. Engineering of a functional human NADH-dependent cytochrome P450 system. Döhr, O., Paine, M.J., Friedberg, T., Roberts, G.C., Wolf, C.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Cytochrome P-450-dependent vasodilator responses to arachidonic acid in the isolated, perfused kidney of the rat. Oyekan, A.O., McGiff, J.C., Quilley, J. Circ. Res. (1991) [Pubmed]
  10. Curcumin activates the aryl hydrocarbon receptor yet significantly inhibits (-)-benzo(a)pyrene-7R-trans-7,8-dihydrodiol bioactivation in oral squamous cell carcinoma cells and oral mucosa. Rinaldi, A.L., Morse, M.A., Fields, H.W., Rothas, D.A., Pei, P., Rodrigo, K.A., Renner, R.J., Mallery, S.R. Cancer Res. (2002) [Pubmed]
  11. Transient induction of cytochromes P450 1A1 and 1B1 in MCF-7 human breast cancer cells by indirubin. Spink, B.C., Hussain, M.M., Katz, B.H., Eisele, L., Spink, D.C. Biochem. Pharmacol. (2003) [Pubmed]
  12. Differential regulation of CYP1A1 and CYP1B1 expression in resveratrol-treated human medulloblastoma cells. Liu, J., Wang, Q., Wu, D.C., Wang, X.W., Sun, Y., Chen, X.Y., Zhang, K.L., Li, H. Neurosci. Lett. (2004) [Pubmed]
  13. Hepatic cytochrome P450 and related drug biotransformation during an outbreak of mouse hepatitis virus in a colony of Swiss BALB/c mice. Armstrong, S., Renton, K.W. Can. J. Physiol. Pharmacol. (1993) [Pubmed]
  14. Effects of hepatic fibrosis on ofloxacin pharmacokinetics in rats. Wang, H., Liao, Z.X., Chen, M., Hu, X.L. Pharmacol. Res. (2006) [Pubmed]
  15. Polyamine biosynthesis and monooxygenase enzyme activity in rat liver cirrhosis and regeneration. Raunio, H., Rautio, A., Arranto, A.J., Saarni, H.U. Res. Commun. Chem. Pathol. Pharmacol. (1986) [Pubmed]
  16. Correlation of placental microsomal activities with protein detected by antibodies to rabbit cytochrome P-450 isozyme 6 in preparations from humans exposed to polychlorinated biphenyls, quaterphenyls, and dibenzofurans. Wong, T.K., Domin, B.A., Bent, P.E., Blanton, T.E., Anderson, M.W., Philpot, R.M. Cancer Res. (1986) [Pubmed]
  17. Biotransformation in carcinogen-induced diploid and polyploid hepatocytes separated by centrifugal elutriation. Watkins, J.B., Thierau, D., Schwarz, L.R. Cancer Res. (1992) [Pubmed]
  18. Methylation of cytochrome P4501A1 promoter in the lung is associated with tobacco smoking. Anttila, S., Hakkola, J., Tuominen, P., Elovaara, E., Husgafvel-Pursiainen, K., Karjalainen, A., Hirvonen, A., Nurminen, T. Cancer Res. (2003) [Pubmed]
  19. Sensitivity of human placental monooxygenase activity to maternal smoking. Manchester, D.K., Jacoby, E.H. Clin. Pharmacol. Ther. (1981) [Pubmed]
  20. Selective induction of rat hepatic CYP1 and CYP4 proteins and of peroxisomal proliferation by green tea. Bu-Abbas, A., Clifford, M.N., Walker, R., Ioannides, C. Carcinogenesis (1994) [Pubmed]
  21. 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline induces and inhibits cytochrome P450 from the IA subfamily in chick and rat hepatocytes. Sinclair, J.F., Schaeffer, B.K., Wood, S.G., Lambrecht, L.K., Gorman, N., Bement, W.J., Smith, E.L., Sinclair, P.R., Waldren, C.A. Cancer Res. (1992) [Pubmed]
  22. Structure-dependent induction of aryl hydrocarbon hydroxylase in human breast cancer cell lines and characterization of the Ah receptor. Harris, M., Piskorska-Pliszczynska, J., Zacharewski, T., Romkes, M., Safe, S. Cancer Res. (1989) [Pubmed]
  23. 3-methylcholanthrene-induced monooxygenase (O-deethylation) activity of human lymphocytes. Burke, M.D., Mayer, R.T., Kouri, R.E. Cancer Res. (1977) [Pubmed]
  24. Uptake and specific binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the olfactory mucosa of mice and rats. Gillner, M., Brittebo, E.B., Brandt, I., Söderkvist, P., Appelgren, L.E., Gustafsson, J.A. Cancer Res. (1987) [Pubmed]
  25. Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture. Langouët, S., Coles, B., Morel, F., Becquemont, L., Beaune, P., Guengerich, F.P., Ketterer, B., Guillouzo, A. Cancer Res. (1995) [Pubmed]
  26. Immunochemical detection and quantitation of microsomal cytochrome P-450 and reduced nicotinamide adenine dinucleotide phosphate:cytochrome P-450 reductase in the rat ventral prostate. Haaparanta, T., Halpert, J., Glaumann, H., Gustafsson, J.A. Cancer Res. (1983) [Pubmed]
  27. Establishment of a Salmonella tester strain highly sensitive to mutagenic heterocyclic amines. Suzuki, A., Kushida, H., Iwata, H., Watanabe, M., Nohmi, T., Fujita, K., Gonzalez, F.J., Kamataki, T. Cancer Res. (1998) [Pubmed]
  28. Small intestinal cytochromes P450. Kaminsky, L.S., Fasco, M.J. Crit. Rev. Toxicol. (1991) [Pubmed]
  29. Cryopreservation of isolated primary rat hepatocytes: enhanced survival and long-term hepatospecific function. Sosef, M.N., Baust, J.M., Sugimachi, K., Fowler, A., Tompkins, R.G., Toner, M. Ann. Surg. (2005) [Pubmed]
  30. Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line. Mills, J.B., Rose, K.A., Sadagopan, N., Sahi, J., de Morais, S.M. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  31. Cerium-induced strain-dependent increase in Cyp2a-4/5 (cytochrome P4502a-4/5) expression in the liver and kidneys of inbred mice. Salonpää, P., Iscan, M., Pasanen, M., Arvela, P., Pelkonen, O., Raunio, H. Biochem. Pharmacol. (1992) [Pubmed]
  32. Cytochrome P-450 1A1 expression in human small bowel: interindividual variation and inhibition by ketoconazole. Paine, M.F., Schmiedlin-Ren, P., Watkins, P.B. Drug Metab. Dispos. (1999) [Pubmed]
  33. Cyp2a6 is a principal enzyme involved in hydroxylation of 1,7-dimethylxanthine, a main caffeine metabolite, in humans. Kimura, M., Yamazaki, H., Fujieda, M., Kiyotani, K., Honda, G., Saruwatari, J., Nakagawa, K., Ishizaki, T., Kamataki, T. Drug Metab. Dispos. (2005) [Pubmed]
  34. Increased expression and decreased activity of cytochrome P450 1A1 in a murine model of toluene diisocyanate-induced asthma. Haag, M., Leusink-Muis, T., Le Bouquin, R., Nijkamp, F.P., Lugnier, A., Frossard, N., Folkerts, G., Pons, F. Arch. Toxicol. (2002) [Pubmed]
  35. Effects of neonatal and adult castration on the in vitro metabolism of steroids and xenobiotics in rat liver. Blanck, A., Aström, A., Hansson, T. Cancer Res. (1986) [Pubmed]
  36. Cytochrome P450 CYP1A1 accumulates in the cytosol of kidney and brain and is activated by heme. Meyer, R.P., Podvinec, M., Meyer, U.A. Mol. Pharmacol. (2002) [Pubmed]
  37. Protection by green tea, black tea, and indole-3-carbinol against 2-amino-3-methylimidazo[4,5-f]quinoline-induced DNA adducts and colonic aberrant crypts in the F344 rat. Xu, M., Bailey, A.C., Hernaez, J.F., Taoka, C.R., Schut, H.A., Dashwood, R.H. Carcinogenesis (1996) [Pubmed]
  38. Dioxinlike components in incinerator fly ash: a comparison between chemical analysis data and results from a cell culture bioassay. Till, M., Behnisch, P., Hagenmaier, H., Bock, K.W., Schrenk, D. Environ. Health Perspect. (1997) [Pubmed]
WikiGenes - Universities