High-throughput screening assays for CYP2B6 metabolism and inhibition using fluorogenic vivid substrates

AAPS PharmSci

Volumn 5, Issue 2, 2003, Pages

  Marks, Bryan D ^a   Goossens, Tony A ^a   Braun, Heidi A ^a   Ozers, Mary S ^a   Smith, Ronald W ^a   Lebakken, Connie ^a   Trubetskoy, Olga V ^a  

^a INVITROGEN CORPORATION   (United States)

Author keywords

CYP2B6; Cytochrome P450; Drug metabolism; Fluorescent substrate; High throughput screening (HTS)

Indexed keywords

ALLYL SULFIDE; AMFEBUTAMONE; AMITRIPTYLINE; CAFFEINE; CLOTRIMAZOLE; CYCLOPHOSPHAMIDE; CYTOCHROME P450 2B6; CYTOCHROME P450 INHIBITOR; CYTOCHROME P450 ISOENZYME; DEXTROMETHORPHAN; DICLOFENAC; DIETHYLDITHIOCARBAMIC ACID; DILTIAZEM; DIMETHYLNITROSAMINE; IBUPROFEN; IMIPRAMINE; KETOCONAZOLE; LIDOCAINE; MEPHENYTOIN; METOPROLOL; MICONAZOLE; MIDAZOLAM; NIFEDIPINE; ORPHENADRINE; PARACETAMOL; PHENETHYL ISOTHIOCYANATE; PROGESTERONE; PROPOFOL; THIAMAZOLE; UNINDEXED DRUG; FLUORESCENT DYE; N DEMETHYLASE; S MEPHENYTOIN N DEMETHYLASE; S-MEPHENYTOIN N-DEMETHYLASE; SOLVENT; UNSPECIFIC MONOOXYGENASE;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG METABOLISM; ENZYMATIC ASSAY; ENZYME INHIBITION; ENZYME KINETICS; ENZYME SUBSTRATE; FLUORESCENCE ANALYSIS; HIGH THROUGHPUT SCREENING; METABOLISM; NONHUMAN; PHARMACOKINETICS; SENSITIVITY AND SPECIFICITY; VALIDATION PROCESS; CHEMISTRY; DRUG ANTAGONISM; DRUG SCREENING; ENZYME SPECIFICITY; METHODOLOGY;

ARYL HYDROCARBON HYDROXYLASES; CHEMISTRY, PHARMACEUTICAL; DRUG EVALUATION, PRECLINICAL; FLUORESCENT DYES; OXIDOREDUCTASES, N-DEMETHYLATING; SOLVENTS; SUBSTRATE SPECIFICITY;

EID: 55449129657     PISSN: 15221060     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (40)

1. Guengerich FP. Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, ed. Cytochrome P450: Structure, Mechanism and Biochemistry. 2nd ed. New York, NY: Plenum Press; 1995:473-535.
2. Raucy JL, Allen SW. Recent advances in P450 research. Pharmacogenomics J. 2001;1:178-186.
3. Lang T, Klein K, Fischer J, et al. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001;11:399-415.
4. Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 1996;6:1-42.
5. Coukell AJ, Markham A. Clopidogrel. Drugs. 1997;54:745-750; discussion 751.
6. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Inter-individual variations in human liver cytochrome P-450 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. 1994;270:414-423.
7. Ekins S, VandenBranden M, Ring BJ, Wrighton SA. Examination of purported probes of human CYP2B6. Pharmacogenetics. 1997;7:165-179.
8. Ekins S, Ring BJ, Binkley SN, Hall SD, Wrighton SA. Autoactivation and activation of the cytochrome P450s. Int J Clin Pharmacol Ther. 1998;36:642-651.
9. Ekins S, Vandenbranden M, Ring BJ, et al. Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther. 1998;286:1253-1259.
10. Gervot L, Rochat B, Gautier JC, et al. Human CYP2B6: expression, inducibility and catalytic activities. Pharmacogenetics. 1999;9:295-306.
11. Granvil CP, Madan A, Sharkawi M, Parkinson A, Wainer IW. Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes. Drug Metab Dispos. 1999;27:533-541.
12. Stevens JC, White RB, Hsu SH, Martinet M. Human liver CYP2B6-catalyzed hydroxylation of RP 73401. J Pharmacol Exp Ther. 1997;282:1389-1395.
13. Faucette SR, Hawke RL, Lecluyse EL, et al. Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos. 2000;28:1222-1230.
14. Kreth K, Kovar K, Schwab M, Zanger UM. Identification of the human cytochromes P450 involved in the oxidative metabolism of "Ecstasy"-related designer drugs. Biochem Pharmacol. 2000;59:1563-1571.
15. Ekins S, Bravi G, Ring BJ, et al. Three-dimensional quantitative structure activity relationship analyses of substrates for CYP2B6. J Pharmacol Exp Ther. 1999;288:21-29.
16. Wang Q, Halpert JR. Combined three-dimensional quantitative structure-activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling. Drug Metab Dispos. 2002;30:86-95.
17. Ekins S, de Groot MJ, Jones JP. Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites. Drug Metab Dispos. 2001;29:936-944.
18. Kariv I, Fereshteh MP, Oldenburg KR. Development of a miniaturized 384-well high throughput screen for the detection of substrates of cytochrome P450 2D6 and 3A4 metabolism. J Biomol Screen. 2001;6:91-99.
19. Miller VP, Stresser DM, Blanchard AP, Turner S, Crespi CL. Fluorometric high-throughput screening for inhibitors of cytochrome P450. Ann N Y Acad Sci. 2000;919:26-32.
20. Stresser DM, Blanchard AP, Turner SD, et al. Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates. Drug Metab Dispos. 2000;28:1440-1448.
21. Chauret N, Dobbs B, Lackman RL, et al. The use of 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) as a specific CYP2D6 probe in human liver microsomes. Drug Metab Dispos. 2001;29:1196-1200.
22. Kent UM, Yanev S, Hollenberg PF. Mechanism-based inactivation of cytochromes P450 2B1 and P450 2B6 by n-propylxanthate. Chem Res Toxicol. 1999;12:317-322.
23. Ariyoshi N, Miyazaki M, Toide K, Sawamura Y, Kamataki T. A single nucleotide polymorphism of CYP2B6 found in Japanese enhances catalytic activity by autoactivation. Biochem Biophys Res Commun. 2001;281:1256-1260.
24. Zlokarnik G. Cytochrome P450 assays for miniaturized formats and library screening in Optimizing Lead Selection (Vol 1) - High Throughput Screening Assays, AdvanceTech Monitor. 2000:37-69.
25. Marks BD, Smith RW, Braun HA, et al. A novel HTS assay to screen for CYP2E1 metabolism and inhibition using a fluorogenic Vivid P450 substrate. ASSAY Drug Devel Technol. 2002;1(1-1):73-81. Available at: http://www.panvera.com/tech/posters/4147_e10_p73-82.pdf.
26. Jinno H, Tanaka-Kagawa T, Ohno A, et al. Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos. 2003;31:398-403.
27. Hiratsuka M, Takekuma Y, Endo N, et al. Allele and genotype frequencies of CYP2B6 and CYP3A5 in the Japanese population. Eur J Clin Pharmacol. 2002;58:417-421.
28. Yuan R, Madani S, Wei XX, Reynolds K, Huang SM. Evaluation of cytochrome p450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metab Dispos. 2002;30:1311-1319.
29. Hesse LM, Venkatakrishnan K, Court MH, et al. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos. 2000;28:1176-1183.
30. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM. Inhibition of cytochrome P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002;30:314-318.
31. Guo Z, Raeissi S, White RB, Stevens JC. Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997;25:390-393.
32. Nakajima M, Yoshida R, Shimada N, Yamazaki H, Yokoi T. Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Drug Metab Dispos. 2001;29:1110-1113.
33. Court MH, Duan SX, Hesse LM, Venkatakrishnan K, Greenblatt DJ. Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology. 2001;94:110-119.
34. Rae JM, Soukhova NV, Flockhart DA, Desta Z. Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug Metab Dispos. 2002;30:525-530.
35. Zhang JH, Chung TD, Oldenburg KR. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen. 1999;4:67-73.
36. Code EL, Crespi CL, Penman BW, Gonzalez FJ, Chang TK, Waxman DJ. Human cytochrome P4502B6: interindividual hepatic expression, substrate specificity, and role in procarcinogen activation. Drug Metab Dispos. 1997;25:985-993.
37. DeLuca JG, Dysart GR, Rasnick D, Bradley MO. A direct, highly sensitive assay for cytochrome P-450 catalyzed O-deethylation using a novel coumarin analog. Biochem Pharmacol. 1988;37:1731-1739.
38. Ito K, Iwatsubo T, Kanamitsu S, Nakajima Y, Sugiyama Y. Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. Annu Rev Pharmacol Toxicol. 1998;38:461-499.
39. Pascussi JM, Gerbal-Chaloin S, Fabre JM, Maurel P, Vilarem MJ. Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation. Mol Pharmacol. 2000;58:1441-1450.
40. Rae JM, Johnson MD, Lippman ME, Flockhart DA. Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. J Pharmacol Exp Ther. 2001;299:849-857.