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Chemical Compound Review

sulfaphenazole     4-amino-N-(2-phenylpyrazol- 3...

Synonyms: Sulfabid, Depocid, Eftolon, Firmazolo, Orisulf, ...
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Disease relevance of sulfaphenazole


High impact information on sulfaphenazole


Biological context of sulfaphenazole

  • Although they differ at only 43 of 490 amino acids, sulfaphenazole (SFZ) is a potent and selective inhibitor of P450 2C9 with an IC50 and a spectrally determined binding constant, KS, of <1 microM [8].
  • Twenty-three new derivatives of sulfaphenazole (SPA) were synthesized to further explore the topology of the active sites of human liver cytochromes P450 of the 2C subfamily and to find new selective inhibitors of these cytochromes [9].
  • These enzymes showed similarities in kinetics of phenytoin hydroxylation and sulphaphenazole inhibition compared with human liver phenytoin hydroxylase [10].
  • By means of purification, N-terminal amino acid sequencing and inhibition by antibodies and sulfaphenazole, we have identified the form of cytochrome P450 primarily responsible for 58C80 hydroxylation in human liver, P450hB20-27, to be a member of the P450 2C9 subfamily [11].
  • After pretreatment with L-NMMA (16 micromol/min) and ibuprofen (1200 mg, orally), sulphaphenazole (6 mg/min) did not substantially inhibit bradykinin-induced vasodilation [12].

Anatomical context of sulfaphenazole


Associations of sulfaphenazole with other chemical compounds


Gene context of sulfaphenazole

  • In addition, when sulfaphenazole was combined with S-mephenytoin, further inhibition of 3alpha-hydroxydesogestrel formation was observed suggesting a possible role for CYP2C19 [14].
  • Sulfaphenazole, flavoxamine, and antibodies raised against purified liver cytochrome P450 (P450) 2C9 that inhibit both CYP2C9- and 2C19-dependent activities, significantly inhibited microsomal oxidations of (+)- and (-)-limonene enantiomers [22].
  • The addition of quinidine, a selective inhibitor of CYP2D6, along with triacetyloleandomycin and sulphaphenazole produced an additional decrease in the rate of NT formation in all but the PM liver, but did not completely eliminate the reaction [23].
  • This assumption was confirmed by inhibition with ketoconazole and ritonavir (two potent inhibitors of CYP3A) whereas sulfaphenazole (2C9 inhibitor) and quinidine (2D6 inhibitor) were inefficient [24].
  • Predictions from kinetic studies on heterologously expressed CYPs are consistent with chemical inhibition studies on human liver microsomes with sulfaphenazole and alpha-naphthoflavone that suggest a greater role for CYP2C9, and a smaller role for CYP1A2, at higher substrate concentrations [25].

Analytical, diagnostic and therapeutic context of sulfaphenazole


  1. Urotensin II-induced hypotensive responses in Wistar-Kyoto (Wky) and spontaneously hypertensive (Shr) rats. Gendron, G., Gobeil, F., Bélanger, S., Gagnon, S., Regoli, D., D'Orléans-Juste, P. Peptides (2005) [Pubmed]
  2. Cytochrome p450 2C inhibition reduces post-ischemic vascular dysfunction. Hunter, A.L., Bai, N., Laher, I., Granville, D.J. Vascul. Pharmacol. (2005) [Pubmed]
  3. Cytochrome P450 epoxygenase gene function in hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling. Pokreisz, P., Fleming, I., Kiss, L., Barbosa-Sicard, E., Fisslthaler, B., Falck, J.R., Hammock, B.D., Kim, I.H., Szelid, Z., Vermeersch, P., Gillijns, H., Pellens, M., Grimminger, F., van Zonneveld, A.J., Collen, D., Busse, R., Janssens, S. Hypertension (2006) [Pubmed]
  4. Cytochrome P450 2C9-induced endothelial cell proliferation involves induction of mitogen-activated protein (MAP) kinase phosphatase-1, inhibition of the c-Jun N-terminal kinase, and up-regulation of cyclin D1. Potente, M., Michaelis, U.R., Fisslthaler, B., Busse, R., Fleming, I. J. Biol. Chem. (2002) [Pubmed]
  5. Nifedipine increases cytochrome P4502C expression and endothelium-derived hyperpolarizing factor-mediated responses in coronary arteries. Fisslthaler, B., Hinsch, N., Chataigneau, T., Popp, R., Kiss, L., Busse, R., Fleming, I. Hypertension (2000) [Pubmed]
  6. Mechanisms of inhibition of tolbutamide metabolism: phenylbutazone, oxyphenbutazone, sulfaphenazole. Pond, S.M., Birkett, D.J., Wade, D.N. Clin. Pharmacol. Ther. (1977) [Pubmed]
  7. Sulfaphenazole derivatives as tools for comparing cytochrome P450 2C5 and human cytochromes P450 2Cs: identification of a new high affinity substrate common to those enzymes. Marques-Soares, C., Dijols, S., Macherey, A.C., Wester, M.R., Johnson, E.F., Dansette, P.M., Mansuy, D. Biochemistry (2003) [Pubmed]
  8. Identification of amino acid substitutions that confer a high affinity for sulfaphenazole binding and a high catalytic efficiency for warfarin metabolism to P450 2C19. Jung, F., Griffin, K.J., Song, W., Richardson, T.H., Yang, M., Johnson, E.F. Biochemistry (1998) [Pubmed]
  9. Synthesis of sulfaphenazole derivatives and their use as inhibitors and tools for comparing the active sites of human liver cytochromes P450 of the 2C subfamily. Ha-Duong, N.T., Dijols, S., Marques-Soares, C., Minoletti, C., Dansette, P.M., Mansuy, D. J. Med. Chem. (2001) [Pubmed]
  10. Site-directed mutation studies of human liver cytochrome P-450 isoenzymes in the CYP2C subfamily. Veronese, M.E., Doecke, C.J., Mackenzie, P.I., McManus, M.E., Miners, J.O., Rees, D.L., Gasser, R., Meyer, U.A., Birkett, D.J. Biochem. J. (1993) [Pubmed]
  11. Cytochrome P450 2C9 is responsible for hydroxylation of the naphthoquinone antimalarial drug 58C80 in human liver. Weaver, R.J., Dickins, M., Burke, M.D. Biochem. Pharmacol. (1993) [Pubmed]
  12. Baseline blood flow and bradykinin-induced vasodilator responses in the human forearm are insensitive to the cytochrome P450 2C9 (CYP2C9) inhibitor sulphaphenazole. Passauer, J., Büssemaker, E., Lässig, G., Pistrosch, F., Fauler, J., Gross, P., Fleming, I. Clin. Sci. (2003) [Pubmed]
  13. Prediction of In Vivo Drug-Drug Interactions from In Vitro Data : Factors Affecting Prototypic Drug-Drug Interactions Involving CYP2C9, CYP2D6 and CYP3A4. Brown, H.S., Galetin, A., Hallifax, D., Houston, J.B. Clinical pharmacokinetics. (2006) [Pubmed]
  14. The role of CYP2C in the in vitro bioactivation of the contraceptive steroid desogestrel. Gentile, D.M., Verhoeven, C.H., Shimada, T., Back, D.J. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  15. Effect of sulfaphenazole on tolbutamide distribution in rabbits: analysis of interspecies differences in tissue distribution of tolbutamide. Sugita, O., Sawada, Y., Sugiyama, Y., Iga, T., Hanano, M. Journal of pharmaceutical sciences. (1984) [Pubmed]
  16. Role of vascular heme oxygenase in reduced myogenic reactivity following chronic hypoxia. Naik, J.S., Walker, B.R. Microcirculation (New York, N.Y. : 1994) (2006) [Pubmed]
  17. The substrate binding site of human liver cytochrome P450 2C9: an NMR study. Poli-Scaife, S., Attias, R., Dansette, P.M., Mansuy, D. Biochemistry (1997) [Pubmed]
  18. Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation. Gentile, D.M., Tomlinson, E.S., Maggs, J.L., Park, B.K., Back, D.J. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  19. Electrochemical characterisation of the human cytochrome P450 CYP2C9. Johnson, D.L., Lewis, B.C., Elliot, D.J., Miners, J.O., Martin, L.L. Biochem. Pharmacol. (2005) [Pubmed]
  20. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Rettie, A.E., Korzekwa, K.R., Kunze, K.L., Lawrence, R.F., Eddy, A.C., Aoyama, T., Gelboin, H.V., Gonzalez, F.J., Trager, W.F. Chem. Res. Toxicol. (1992) [Pubmed]
  21. Studies of flurbiprofen 4'-hydroxylation. Additional evidence suggesting the sole involvement of cytochrome P450 2C9. Tracy, T.S., Marra, C., Wrighton, S.A., Gonzalez, F.J., Korzekwa, K.R. Biochem. Pharmacol. (1996) [Pubmed]
  22. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Miyazawa, M., Shindo, M., Shimada, T. Drug Metab. Dispos. (2002) [Pubmed]
  23. Cytochromes P450 mediating the N-demethylation of amitriptyline. Ghahramani, P., Ellis, S.W., Lennard, M.S., Ramsay, L.E., Tucker, G.T. British journal of clinical pharmacology. (1997) [Pubmed]
  24. Oxidative metabolism of amprenavir in the human liver. Effect of the CYP3A maturation. Tréluyer, J.M., Bowers, G., Cazali, N., Sonnier, M., Rey, E., Pons, G., Cresteil, T. Drug Metab. Dispos. (2003) [Pubmed]
  25. Human cytochromes P450 mediating phenacetin O-deethylation in vitro: validation of the high affinity component as an index of CYP1A2 activity. Venkatakrishnan, K., von Moltke, L.L., Greenblatt, D.J. Journal of pharmaceutical sciences. (1998) [Pubmed]
  26. Effect of pH and small inorganic ions on binding of sulfadimethoxine and sulfaphenazole to human serum albumin measured by circular dichroism. Otagiri, M., Nakamura, H., Imamura, Y., Matsumoto, U., Fleitman, J., Perrin, J.H. Chem. Pharm. Bull. (1989) [Pubmed]
  27. Identification of a cytochrome P450 2C9-derived endothelium-derived hyperpolarizing factor in essential hypertensive patients. Taddei, S., Versari, D., Cipriano, A., Ghiadoni, L., Galetta, F., Franzoni, F., Magagna, A., Virdis, A., Salvetti, A. J. Am. Coll. Cardiol. (2006) [Pubmed]
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