Selective and potent inhibition of human CYP2C19 activity by a conformationally targeted antipeptide antibody

Drug Metabolism and Disposition

Volumn 28, Issue 7, 2000, Pages 715-717

  Schulz Utermoehl, Timothy ^a   Mountfield, Richard J ^a   Madsen, Kjeld ^a   Jørgensen, Peer N ^a   Hansen, Kristian T ^a  

^a NOVO NORDISK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

4 NITROPHENOL; 4' HYDROXYMEPHENYTOIN; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; ETHOXYRESORUFIN; ETHOXYRESORUFIN DEETHYLASE; IMMUNOGLOBULIN G; MEPHENYTOIN; OXIDOREDUCTASE; OXYGENASE; PACLITAXEL; PEPTIDE ANTIBODY; TOLBUTAMIDE;

ANTIBODY PRODUCTION; ANTIBODY SPECIFICITY; ARTICLE; BINDING AFFINITY; DRUG METABOLISM; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; HUMAN CELL; IMMUNOBLOTTING; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL; PROTEIN TARGETING; RABBIT;

AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES; ARYL HYDROCARBON HYDROXYLASES; BLOTTING, WESTERN; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; MIXED FUNCTION OXYGENASES; PEPTIDES; PROTEIN CONFORMATION; RABBITS; RECOMBINANT PROTEINS;

ORYCTOLAGUS CUNICULUS;

EID: 0033942763     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (14)

1. Burke MD and Mayer RT (1983) Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its N-alkyl ethers (alkoxyresorufins). Chem Biol Interact 45:243-258.
2. Edwards RJ, Adams DA, Watts PS, Davies DS and Boobis AR (1998) Development of a comprehensive panel of antibodies against the major xenobiotic metabolising forms of cytochrome P450 in humans. Biochem Pharmacol 56:377-387.
3. Goldstein JA and de Morais SMF (1994) Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 4:285-299.
4. Goldstein JA, Ishizaki T, Chiba K, de Morais SM, Bell D, Krahn PM and Evans DA (1997) Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metaboliser phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 7:59-64.
5. Jones DR, Gorski JC, Hamman MA and Hall SD (1996) Quantification of dextromethorphan and metabolites: A dual phenotypic marker for cytochrome P4503A4/5 and 2D6 activity. J Chromatogr 678:105-111.
6. Lasker JM, Wester MR, Aramsombatdee E and Raucy JL (1998) Characterisation of CYP2C19 and CYP2C9 from human liver: Respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys 353:16-28.
7. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC and Nebert DW (1996) P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1-42.
8. Pritchard PM, Glancey MJ, Blake JAR, Gilham DE, Burchell B, Wolf CR and Friedberg T (1998) Functional co-expression of CYP2D6 and human NADPH-cytochrome P450 reductase in Escherichia coli. Pharmacogenetics 8: 33-42.
9. Richardson TH, Griffin KJ, Jung F, Raucy JL and Johnson EF (1997) Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C5. Arch Biochem Biophys 338:157-164.
10. Romkes M, Faletto MB, Blaisdell JA, Raucy JL and Goldstein JA (1991) Cloning and expression of complementary DNAs for multiple members of the human cytochrome P45011C subfamily. Biochemistry 30:3247-3255.
11. Schulz-Utermoehl T, Boobis AR and Edwards RJ (2000) The affinity and potency of proinhibitory antipeptide antibodies towards CYP2D6 is enhanced using cyclic peptides as immunogens. Drug Metab Dispos 28:544-551.
12. Shimada T, Yamazaki H, Mimura M, Inui Y and Guengerich FP (1994) Interindividual variations in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-422.
13. Wedlund PJ, Aslanian WS, McAllister CB, Wilkinson GR and Branch RA (1984) Mephenytoin hydroxylation deficiency in Caucasians: Frequency of a new oxidative drug metabolism polymorphism. Clin Phamacol Ther 36:773-780.
14. Wrighton SA, Stevens JC, Becker GW and Van den Branden M (1993) Isolation and characterisation of human liver cytochrome P450 2C19: Correlation between 2C19 and. S-mephenytoin 4′-hydroxylation Arch Biochem Biophys 306:240-245.