Application of cytochrome P450 drug interaction screening in drug discovery

Combinatorial Chemistry and High Throughput Screening

Volumn 13, Issue 2, 2010, Pages 145-158

  Foti, Robert S ^a   Wienkers, Larry C ^a   Wahlstrom, Jan L ^a  

^a AMGEN INC   (United States)

Author keywords

Drug interactions; Enzyme inhibition; In silico; P450

Indexed keywords

AMFEBUTAMONE; AMODIAQUINE; BUFURALOL; CHLORZOXAZONE; COUMARIN; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2A6; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 2E1; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DEXTROMETHORPHAN; DICLOFENAC; MEPHENYTOIN; MIDAZOLAM; OMEPRAZOLE; PACLITAXEL; PARACETAMOL; PHENACETIN; RADAFAXINE; TESTOSTERONE; WARFARIN;

COMPUTER MODEL; DRUG BIOAVAILABILITY; DRUG COMPETITION; DRUG DETERMINATION; DRUG INTERACTION; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME METABOLISM; ENZYME SUBSTRATE; PATIENT SAFETY; PHARMACOGENETICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DISCOVERY; DRUG INTERACTIONS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS;

EID: 77949788280     PISSN: 13862073     EISSN: None     Source Type: Journal    
DOI: 10.2174/138620710790596718     Document Type: Review

References (140)

1. Kunze, K.L.; Wienkers, L.C.; Thummel, K.E.; Trager, W.F. Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab. Dispos., 1996, 24(4), 414-421.
2. Wienkers, L.C.; Steenwyk, R.C.; Sanders, P.E.; Pearson, P.G. Biotransformation of tirilazad in human: 1. Cytochrome P450 3A-mediated hydroxylation of tirilazad mesylate in human liver microsomes. J. Pharmacol. Exp. Ther., 1996, 277(2), 982-990.
3. Bu, H.Z.; Knuth, K.; Magis, L.; Teitelbaum, P. High-throughput cytochrome P450 (CYP) inhibition screening via cassette probe-dosing strategy: III. Validation of a direct injection/on-line guard cartridge extraction-tandem mass spectrometry method for CYP2C19 inhibition evaluation. J. Pharm. Biomed. Anal., 2001, 25(3-4), 437-442.
4. Walsky, R.L.; Obach, R.S. Validated assays for human cytochrome P450 activities. Drug Metab. Dispos., 2004, 32(6), 647-660.
5. Yao, M.; Zhu, M.; Sinz, M.W.; Zhang, H.; Humphreys, W.G.; Rodrigues, A.D.; Dai, R. Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysis. J. Pharm. Biomed. Anal., 2007, 44(1), 211-223.
6. Bjornsson, T.D.; Callaghan, J.T.; Einolf, H.J.; Fischer, V.; Gan, L.; Grimm, S.; Kao, King, J.; S.P.; Miwa, G.; Ni, L.; Kumar, G.; McLeod, J.; Obach, R.S.; Roberts, S.; Roe, A.; Shah, A.; Snikeris, F.; Sullivan, J.T.; Tweedie, D.; Vega, J.M.; Walsh, J.; Wrighton, S.A. The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab. Dispos., 2003, 31(7), 815-832.
7. Yuan, R.; Madani, S.; Wei, X.X.; Reynolds, K.; Huang, S.M. Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metab. Dispos., 2002, 30(12), 1311-1319.
8. Wynalda, M.A.; Wienkers, L.C. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab. Dispos., 1997, 25(10), 1211-1214.
9. Labrie, P.; Maddaford, S.P.; Lacroix, J.; Catalano, C.; Lee, D.K.; Rakhit, S.; Gaudreault, R.C. In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2). Bioorg. Med. Chem., 2007, 15(11), 3854-3868.
10. Velaparthi, U.; Liu, P.; Balasubramanian, B.; Carboni, J.; Attar, R.; Gottardis, M.; Li, A.; Greer, A.; Zoeckler, M.; Wittman, M.D.; Vyas, D. Imidazole moiety replacements in the 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)- one inhibitors of insulin-like growth factor receptor-1 (IGF-1R) to improve cytochrome P450 profile. Bioorg. Med. Chem. Lett., 2007, 17(11), 3072-3076.
11. Krippendorff, B.F.; Lienau, P.; Reichel, A.; Huisinga, W. Optimizing classification of drug-drug interaction potential for CYP450 isoenzyme inhibition assays in early drug discovery. J. Biomol. Screen., 2007, 12(1), 92-99.
12. Bachmann, K.A.; Lewis, J.D. Predicting inhibitory drug-drug interactions and evaluating drug interaction reports using inhibition constants. Ann. Pharmacother., 2005, 39(6), 1064-1072.
13. Blanchard, N.; Richert, L.; Coassolo, P.; Lave, T. Qualitative and quantitative assessment of drug-drug interaction potential in man, based on Ki, IC50 and inhibitor concentration. Curr. Drug Metab., 2004, 5(2), 147-156.
14. Kanamitsu, S.; Ito, K.; Sugiyama, Y. Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics: use of maximum unbound concentration of inhibitor at the inlet to the liver. Pharm. Res., 2000, 17(3), 336-343.
15. Venkatakrishnan, K.; Obach, R.S. Drug-drug interactions via mechanism-based cytochrome P450 inactivation: points to consider for risk assessment from in vitro data and clinical pharmacologic evaluation. Curr. Drug Metab., 2007, 8(5), 449-462.
16. Chandra, P.; Brouwer, K.L. The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm. Res., 2004, 21(5), 719-735.
17. Kiang, T.K.; Ensom, M.H.; Chang, T.K. UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol. Ther., 2005, 106(1), 97-132.
18. Williams, J.A.; Hyland, R.; Jones, B.C.; Smith, D.A.; Hurst, S.; Goosen, T.C.; Peterkin, V.; Koup, J.R.; Ball, S.E. Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab. Dispos., 2004, 32(11), 1201-1208.
19. Noe, J.; Portmann, R.; Brun, M.E.; Funk, C. Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab. Dispos., 2007, 35(8), 1308-1314.
20. Natarajan, C.; Rohatagi, S. In: Bonate, P., Howard, D., Eds.; Role of Preclinical Pharmacokinetics in Drug Development, in Pharmacokinetics in Drug Development: Regulatory and Development Paradigms, Springer: New York. 2004, p. 136.
21. Houston, J.B.; Kenworthy, K.E.; Galetin, A. In: Lee, J.S., Obach, R.S., Fisher, M.B., Eds.; Typical and Atypical Enzyme Kinetics, in Drug Metabolizing Enzymes: Cytochrome P450 and Other Enzymes in Drug Discovery and Development, Marcel Dekker, Inc.: New York. 2003, p. 211-254.
22. Kashuba, A.D.M.; Park, J.J.; Persky, A.M.; Brouwer, K.L.R. In: Burton, M.E., Ed.; Drug Metabolism, Transport, and the Influence of Hepatic Disease, in Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring, Lippincott Williams & Wilkins: Philadelphia. 2006, p. 151-152.
23. Segel, I.H.; Simple Inhibition Systems, in Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. John Wiley & Sons, Inc.: New York. 1975, p. 111.
24. Tucker, G.T.; Houston, J.B.; Huang, S.M. EUFEPS conference report. Optimising drug development: strategies to assess drug metabolism/transporter interaction potential - towards a consensus. European Federation of Pharmaceutical Sciences. Eur. J. Pharm. Sci., 2001, 3(4), 417-428.
25. Fukushima, Y.; Ushimaru, M.; Takahara, S. On the error of the dixon plot for estimating the inhibition constant between enzyme and inhibitor. Biochem. Mol. Biol. Educ., 2002, 30(2), 90-92.
26. Gao, F.; Johnson, D.L.; Ekins, S.; Janiszewski, J.; Kelly, K.G.; Meyer, R.D.; West, M. Optimizing higher throughput methods to assess drug-drug interactions for CYP1A2, CYP2C9, CYP2C19, CYP2D6, rCYP2D6, and CYP3A4 in vitro using a single point IC(50). J. Biomol. Screen., 2002, 7(4), 373-382.
27. Cheng, Y.; Prusoff, W.H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol., 1973, 22(23), 3099-3108.
28. von Moltke, L.L.; Greenblatt, D.J.; Schmider, J.; Wright, C.E.; Harmatz, J.S.; and Shader, R.I. In vitro approaches to predicting drug interactions in vivo. Biochem. Pharmacol., 1998, 55(2), 113-122.
29. McGinnity, D.F.; Griffin, S.J.; Moody, G.C.; Voice, M.; Hanlon, S.; Friedberg, T.; Riley, R.J. Rapid characterization of the major drug-metabolizing human hepatic cytochrome P-450 enzymes expressed in Escherichia coli. Drug Metab. Dispos., 1999, 27(9), 1017-1023.
30. Di, L.; Kerns, E.H.; Li, S.Q.; Carter, G.T. Comparison of cytochrome P450 inhibition assays for drug discovery using human liver microsomes with LC-MS, rhCYP450 isozymes with fluorescence, and double cocktail with LC-MS. Int. J. Pharm., 2007, 335(1-2), 1-11.
31. Crespi, C.L.; Miller, V.P. The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics, 1997, 7(3), 203-210.
32. Kumar, V.; Rock, D.A.; Warren, C.J.; Tracy, T.S.; Wahlstrom, J.L. Enzyme source effects on CYP2C9 kinetics and inhibition. Drug Metab. Dispos., 2006, 34(11), 1903-1908.
33. McGinnity, D.F.; Tucker, J.; Trigg, S.; Riley, R.J. Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes. Drug Metab. Dispos., 2005, 33(11), 1700-1707.
34. Rodrigues, A.D.; Lin, J.H. Screening of drug candidates for their drug - drug interaction potential. Curr. Opin. Chem. Biol., 2001, 5(4), 396-401.
35. Brown, H.S.; Chadwick, A.; Houston, J.B. Use of isolated hepatocyte preparations for cytochrome P450 inhibition studies: comparison with microsomes for Ki determination. Drug Metab. Dispos., 2007, 35(11), 2119-2126.
36. Cohen, L.H.; Remley, M.J.; Raunig, D.; Vaz, A.D. In vitro drug interactions of cytochrome p450: an evaluation of fluorogenic to conventional substrates. Drug Metab. Dispos., 2003, 31(8), 1005-1015.
37. Galetin, A.; Clarke, S.E.; Houston, J.B. Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates: midazolam, testosterone, and nifedipine. Drug Metab. Dispos., 2003, 31(9), 1108-1116.
38. Wang, R.W.; Newton, D.J.; Liu, N.; Atkins, W.M.; Lu, A.Y. Human cytochrome P-450 3A4: in vitro drug-drug interaction patterns are substrate-dependent. Drug Metab. Dispos., 2000, 28(3), 360-366.
39. Schrag, M.L.; Wienkers, L.C. Covalent alteration of the CYP3A4 active site: evidence for multiple substrate binding domains. Arch. Biochem. Biophys., 2001, 391(1), 49-55.
40. Williams, P.A.; Cosme, J.; Ward, A.; Angove, H.C.; Vinkovic, D. M.; Jhoti, H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature, 2003, 424(6947), 464-468.
41. Yano, J.K.; Wester, M.R.; Schoch, G.A.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution. J. Biol. Chem., 2004, 279(37), 38091-38094.
42. Galetin, A.; Ito, K.; Hallifax, D.; Houston, J.B. CYP3A4 substrate selection and substitution in the prediction of potential drug-drug interactions. J. Pharmacol. Exp. Ther., 2005, 314(1), 180-190.
43. Kumar, V.; Wahlstrom, J.L.; Rock, D.A.; Warren, C.J.; Gorman, L.A.; Tracy, T.S. CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab. Dispos., 2006, 34(12), 1966-1975.
44. Foti, R.S.; Wahlstrom, J.L. CYP2C19 Inhibition: The Impact of Substrate Probe Selection on In vitro Inhibition Profiles. Drug Metab. Dispos., 2007.
45. Hummel, M.A.; Tracy, T.S.; Hutzler, J.M.; Wahlstrom, J.L.; Zhou, Y.; Rock, D.A. Influence of fluorescent probe size and cytochrome b5 on drug-drug interactions in CYP2C9. J. Biomol. Screen., 2006, 11(3), 303-309.
46. Sudsakorn, S.; Skell, J.; Williams, D.A.; O'Shea, T.J.; Liu, H. Evaluation of 3-O-methylfluorescein as a selective fluorometric substrate for CYP2C19 in human liver microsomes. Drug Metab. Dispos., 2007, 35(6), 841-847.
47. Hutzler, M.; Messing, D.M.; Wienkers, L.C. Predicting drug-drug interactions in drug discovery: where are we now and where are we going? Curr. Opin. Drug Discov. Devel., 2005, 8(1), 51-58.
48. Jansson, I.; Schenkman, J.B. Substrate influence on interaction between cytochrome P450 and cytochrome b5 in microsomes. Arch. Biochem. Biophys., 1996, 325(2), 265-269.
49. Vergeres, G.; Waskell, L. Cytochrome b5, its functions, structure and membrane topology. Biochimie, 1995, 77(7-8), 604-620.
50. Schenkman, J.B.; Jansson, I. The many roles of cytochrome b5. Pharmacol. Ther., 2003, 97(2), 139-152.
51. Locuson, C.W.; Wienkers, L.C.; Jones, J.P.; Tracy, T.S. CYP2C9 protein interactions with cytochrome b(5): effects on the coupling of catalysis. Drug Metab. Dispos., 2007, 35(7), 1174-1181.
52. Venkatakrishnan, K.; von Moltke, L.L.; Court, M.H.; Harmatz, J.S.; Crespi, C.L.; Greenblatt, D.J. Comparison between cytochrome P450 (CYP) content and relative activity approaches to scaling from cDNA-expressed CYPs to human liver microsomes: ratios of accessory proteins as sources of discrepancies between the approaches. Drug Metab. Dispos., 2000, 28(12), 1493-1504.
53. Yamazaki, H.; Shimada, T.; Martin, M.V.; Guengerich, F.P. Stimulation of cytochrome P450 reactions by apo-cytochrome b5: evidence against transfer of heme from cytochrome P450 3A4 to apo-cytochrome b5 or heme oxygenase. J. Biol. Chem., 2001, 276(33), 30885-30891.
54. Foti, R.S.; Fisher, M.B. Impact of incubation conditions on bufuralol human clearance predictions: enzyme lability and nonspecific binding. Drug Metab. Dispos., 2004, 32(3), 295-304.
55. Margolis, J.M.; Obach, R.S. Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502D6: implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metab. Dispos., 2003, 31(5), 606-611.
56. Umeda, S.; Harakawa, N.; Yamamoto, M.; Ueno, K. Effect of nonspecific binding to microsomes and metabolic elimination of buprenorphine on the inhibition of cytochrome P4502D6. Biol. Pharm. Bull., 2005, 28(2), 212-216.
57. Baba, T.; Touchi, A.; Ito, K.; Yamaguchi, Y.; Yamazoe, Y.; Ohno, Y.; Sugiyama, Y. Effects of serum albumin and liver cytosol on CYP2C9- and CYP3A4-mediated drug metabolism. Drug Metab. Pharmacokinet., 2002, 17(6), 522-531.
58. Lu, C.; Miwa, G.T.; Prakash, S.R.; Gan, L.S.; Balani, S.K. A novel model for the prediction of drug-drug interactions in humans based on in vitro cytochrome p450 phenotypic data. Drug Metab. Dispos., 2007, 35(1), 79-85.
59. Skaggs, S.M.; Foti, R.S.; Fisher, M.B. A streamlined method to predict hepatic clearance using human liver microsomes in the presence of human plasma. J. Pharmacol. Toxicol. Methods, 2006, 53(3), 284-290.
60. Yao, C.; Levy, R.H. Inhibition-based metabolic drug-drug interactions: predictions from in vitro data. J. Pharm. Sci., 2002, 91(9), 1923-1935.
61. Yamazaki, H.; Ueng, Y.F.; Shimada, T.; Guengerich, F.P. Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH - cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates. Biochemistry, 1995, 34(26), 8380-8389.
62. Schrag, M.L.; Wienkers, L.C. Topological alteration of the CYP3A4 active site by the divalent cation Mg(2+). Drug Metab. Dispos., 2000, 28(10), 1198-1201.
63. Busby, W.F.; Jr., Ackermann, J.M.; Crespi, C.L. Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro activities of cDNA-expressed human cytochromes P-450. Drug Metab. Dispos., 1999, 27(2), 246-249.
64. Easterbrook, J.; Lu, C.; Sakai, Y.; Li, A.P. Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metab. Dispos., 2001, 29(2), 141-144.
65. Hickman, D.; Wang, J.P.; Wang, Y.; Unadkat, J.D. Evaluation of the selectivity of In vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metab. Dispos., 1998, 26(3), 207-215.
66. Chauret, N.; Gauthier, A.; Nicoll-Griffith, D.A. Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metab. Dispos., 1998, 26(1), 1-4.
67. Vuppugalla, R.; Chang, S.Y.; Zhang, H.; Marathe, P.H.; Rodrigues, D.A. Effect of commonly used organic solvents on the kinetics of cytochrome P450 2B6- and 2C8-dependent activity in human liver microsomes. Drug Metab. Dispos., 2007, 35(11), 1990-1995.
68. Tang, C.; Shou, M.; Rodrigues, A.D. Substrate-dependent effect of acetonitrile on human liver microsomal cytochrome P450 2C9 (CYP2C9) activity. Drug Metab. Dispos., 2000, 28(5), 567-572.
69. Iwase, M.; Kurata, N.; Ehana, R.; Nishimura, Y.; Masamoto, T.; Yasuhara, H. Evaluation of the effects of hydrophilic organic solvents on CYP3A-mediated drug-drug interaction in vitro. Hum. Exp. Toxicol., 2006, 25(12), 715-721.
70. Shen, H.; He, M.M.; Liu, H.; Wrighton, S.A.; Wang, L.; Guo, B.; Li, C. Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug Metab. Dispos., 2007, 35(8), 1292-1300.
71. Ingelman-Sundberg, M.; Sim, S.C.; Gomez, A.; Rodriguez-Antona, C. Influence of cytochrome P450 polymorphisms on drug therapies: Pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol. Ther., 2007, 116(3), 496-526.
72. Pirmohamed, M.; Park, B.K. Cytochrome P450 enzyme polymorphisms and adverse drug reactions. Toxicology, 2003, 192(1), 23-32.
73. Rettie, A.E.; Jones, J.P. Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics. Annu. Rev. Pharmacol. Toxicol., 2005, 45, 477-494.
74. Gibbs, M.A.; Thummel, K.E.; Shen, D.D.; Kunze, K.L. Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression. Drug Metab. Dispos., 1999, 27(2), 180-187.
75. Isoherranen, N.; Ludington, S.R.; Givens, R.C.; Lamba, J.K.; Pusek, S.N.; Dees, E.C.; Blough, D.K.; Iwanaga, K.; Hawke, R.L.; Schuetz, E.G.; Watkins, P.B.; Thummel, K.E.; Paine, M.F. The Influence of Cyp3a5 Expression on the Extent of Hepatic Cyp3a Inhibition Is Substrate-Dependent: an in vitro-in vivo Evaluation. Drug Metab. Dispos., 2008, 36(1), 149-154.
76. Foti, R.S.; Fisher, M.B. Importance of patient selection when determining the significance of the CYP3A5 polymorphism in clinical trials. Pharmacogenomics J., 2004, 4(6), 362-364.
77. Thervet, E.; Anglicheau, D.; King, B.; Schlageter, M.H.; Cassinat, B.; Beaune, P.; Legendre, C.; Daly, A.K. Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients. Transplantation, 2003, 76(8), 1233-1235.
78. Crespi, C.L.; Miller, V.P.; Stresser, D.M. Design and application of fluorometric assays for human cytochrome P450 inhibition. Methods Enzymol., 2002, 357, 276-284.
79. Donato, M.T.; Jimenez, N.; Castell, J.V.; Gomez-Lechon, M.J. Fluorescence-based assays for screening nine cytochrome P450 (P450) activities in intact cells expressing individual human P450 enzymes. Drug Metab. Dispos., 2004, 32(7), 699-706.
80. Delaporte, E.; Slaughter, D.E.; Egan, M.A.; Gatto, G.J.; Santos, A.; Shelley, J.; Price, E.; Howells, L.; Dean, D.C.; Rodrigues, A.D. The potential for CYP2D6 inhibition screening using a novel scintillation proximity assay-based approach. J. Biomol. Screen., 2001, 6(4), 225-231.
81. Di Marco, A.; Cellucci, A.; Chaudhary, A.; Fonsi, M. Laufer, R. High-throughput radiometric CYP2C19 inhibition assay using tritiated (S)-mephenytoin. Drug Metab. Dispos., 2007, 35(10), 1737-1743.
82. Moody, G.C.; Griffin, S.J.; Mather, A.N.; McGinnity, D.F.; Riley, R.J. Fully automated analysis of activities catalysed by the major human liver cytochrome P450 (CYP) enzymes: assessment of human CYP inhibition potential. Xenobiotica, 1999, 29(1), 53-75.
83. He, F.; Bi, H.C.; Xie, Z.Y.; Zuo, Z.; Li, J.K.; Li, X.; Zhao, L.Z.; Chen, X. Huang, M. Rapid determination of six metabolites from multiple cytochrome P450 probe substrates in human liver microsome by liquid chromatography/mass spectrometry: application to high-throughput inhibition screening of terpenoids. Rapid Commun. Mass Spectrom., 2007, 21(5), 635-643.
84. Kim, M.J.; Kim, H.; Cha, I.J.; Park, J.S.; Shon, J.H.; Liu, K.H.; Shin, J.G. High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom., 2005, 19(18), 2651-2658.
85. Peng, S.X.; Barbone, A.G.; Ritchie, D.M. High-throughput cytochrome p450 inhibition assays by ultrafast gradient liquid chromatography with tandem mass spectrometry using monolithic columns. Rapid Commun. Mass Spectrom., 2003, 17(6), 509-518.
86. Turpeinen, M.; Korhonen, L.E.; Tolonen, A.; Uusitalo, J.; Juvonen, R.; Raunio, H.; Pelkonen, O. Cytochrome P450 (CYP) inhibition screening: comparison of three tests. Eur. J. Pharm. Sci., 2006, 29(2), 130-138.
87. Crespi, C.L.; Miller, V.P.; Penman, B.W. Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. Anal. Biochem., 1997, 248(1), 188-190.
88. Friden, M.; Vanaja, K.; Nandi, V.N. Drug-drug interactions of anti-infective drugs: utility of fluorescence cyp inhibition assays in drug discovery. Drug Metabol. Drug Interact., 2006, 21(3-4), 163-185.
89. Stresser, D.M.; Blanchard, A.P.; Turner, S.D.; Erve, J.C.; Dandeneau, A.A.; Miller, V.P.; Crespi, C.L. Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates. Drug Metab. Dispos., 2000, 28(12), 1440-1448.
90. Trubetskoy, O.V.; Gibson, J.R.; Marks, B.D. Highly miniaturized formats for in vitro drug metabolism assays using vivid fluorescent substrates and recombinant human cytochrome P450 enzymes. J. Biomol. Screen., 2005, 10(1), 56-66.
91. Cali, J.J.; Ma, D.; Sobol, M.; Simpson, D.J.; Frackman, S.; Good, T.D. Daily, W.J. Liu, D. Luminogenic cytochrome P450 assays. Expert Opin. Drug Metab. Toxicol., 2006, 2(4), 629-645.
92. Didenko, V.V.; Hornsby, P.J. A quantitative luminescence assay for nonradioactive nucleic acid probes. J. Histochem. Cytochem., 1996, 44(6), 657-660.
93. Hutzler, J.M.; Wienkers, L.C.; Wahlstrom, J.L.; Carlson, T.J.; Tracy, T.S. Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations. Arch. Biochem. Biophys., 2003, 410(1), 16-24.
94. Jushchyshyn, M.I.; Hutzler, J.M.; Schrag, M.L.; Wienkers, L.C. Catalytic turnover of pyrene by CYP3A4: evidence that cytochrome B5 directly induces positive cooperativity. Arch. Biochem. Biophys., 2005, 438(1), 21-28.
95. Hiller, D.L.; Brockman, A.H.; Goulet, L.; Ahmed, S.; Cole, R.O.; Covey, T. Application of a non-indexed dual sprayer pneumatically assisted electrospray source to the high throughput quantitation of target compounds in biological fluids. Rapid Commun. Mass Spectrom., 2000, 14(21), 2034-2038.
96. Fung, E.N.; Chu, I.; Li, C.; Liu, T.; Soares, A.; Morrison, R.; Nomeir, A.A. Higher-throughput screening for Caco-2 permeability utilizing a multiple sprayer liquid chromatography/tandem mass spectrometry system. Rapid Commun. Mass Spectrom., 2003, 17(18), 2147-2152.
97. Zimmer, D.; Pickard, V.; Czembor, W.; Muller, C. Comparison of turbulent-flow chromatography with automated solid-phase extraction in 96-well plates and liquid-liquid extraction used as plasma sample preparation techniques for liquid chromatography-tandem mass spectrometry. J. Chromatogr. A., 1999, 854(1-2), 23-35.
98. Lindqvist, A.; Hilke, S.; Skoglund, E. Generic three-column parallel LC-MS/MS system for high-throughput in vitro screens. J. Chromatogr. A., 2004, 1058(1-2), 121-126.
99. Briem, S.; Pettersson, B.; Skoglund, E. Description and validation of a four-channel staggered LC-MS/MS system for high-throughput in vitro screens. Anal. Chem., 2005, 77(6), 1905-1910.
100. Frye, R.F.; Matzke, G.R.; Adedoyin, A.; Porter, J.A.; Branch, R.A. Validation of the five-drug "Pittsburgh cocktail" approach for assessment of selective regulation of drug-metabolizing enzymes. Clin. Pharmacol. Ther., 1997, 62(4), 365-376.
101. Dierks, E.A.; Stams, K.R.; Lim, H.K.; Cornelius, G.; Zhang, H.; Ball, S.E. A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. Drug Metab. Dispos., 2001, 29(1), 23-29.
102. Tolonen, A.; Petsalo, A.; Turpeinen, M.; Uusitalo, J.; Pelkonen, O. In vitro interaction cocktail assay for nine major cytochrome P450 enzymes with 13 probe reactions and a single LC/MSMS run: analytical validation and testing with monoclonal anti-CYP antibodies. J, Mass Spectrom., 2007, 42(7), 960-966.
103. Turpeinen, M.; Uusitalo, J.; Jalonen, J.; Pelkonen, O. Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay. Eur. J. Pharm. Sci., 2005, 24(1), 123-132.
104. Weaver, R.; Graham, K.S.; Beattie, I.G.; Riley, R.J. Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation. Drug Metab. Dispos., 2003, 31(7), 955-966.
105. Hatakeyama, T.; Chen, D.L.; Ismagilov, R.F. Microgram-scale testing of reaction conditions in solution using nanoliter plugs in microfluidics with detection by MALDI-MS. J. Am. Chem. Soc., 2006, 128(8), 2518-2519.
106. Whitesides, G.M.; The origins and the future of microfluidics. Nature, 2006, 442(7101), 368-373.
107. Ozbal, C.C.; LaMarr, W.A.; Linton, J.R.; Green, D.F.; Katz, A.; Morrison, T.B.; Brenan, C.J. High throughput screening via mass spectrometry: a case study using acetylcholinesterase. Assay Drug Dev. Technol., 2004, 2(4), 373-381.
108. Quercia, A.K.; LaMarr, W.A.; Myung, J.; Ozbal, C.C.; Landro, J.A.; Lumb, K.J. High-throughput screening by mass spectrometry: comparison with the scintillation proximity assay with a focused-file screen of AKT1/PKB alpha. J. Biomol. Screen, 2007, 12(4), 473-480.
109. Roddy, T.P.; Horvath, C.R.; Stout, S.J.; Kenney, K.L.; Ho, P.I.; Zhang, J.H.; Vickers, C.; Kaushik, V. Hubbard, B. Wang, Y.K. Mass spectrometric techniques for label-free high-throughput screening in drug discovery. Anal. Chem., 2007, 79(21), 8207-8213.
110. Corr, J.J.; Kovarik, P.; Schneider, B.B.; Hendrikse, J.; Loboda, A.; Covey, T.R. Design considerations for high speed quantitative mass spectrometry with MALDI ionization. J. Am. Soc. Mass Spectrom., 2006, 17(8), 1129-1141.
111. Sleno, L.; Volmer, D.A. Some fundamental and technical aspects of the quantitative analysis of pharmaceutical drugs by matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun. Mass Spectrom., 2005, 19(14), 1928-1936.
112. Wu, J.; Hughes, C.S.; Picard, P.; Letarte, S.; Gaudreault, M.; Levesque, J.F.; Nicoll-Griffith, D.A.; Bateman, K.P. High-throughput cytochrome P450 inhibition assays using laser diode thermal desorption-atmospheric pressure chemical ionization-tandem mass spectrometry. Anal. Chem., 2007, 79(12), 4657-4665.
113. Chang, T.K.; Crespi, C.L.; Waxman, D.J. Determination of CYP2B6 component of 7-ethoxy-4-trifluoromethylcoumarin O-deethylation activity in human liver microsomes. Methods Mol. Biol., 2006, 320, 97-102.
114. Marks, B.D.; Goossens, T.A.; Braun, H.A.; Ozers, M.S.; Smith, R.W.; Lebakken, C.; Trubetskoy, O.V. High-throughput screening assays for CYP2B6 metabolism and inhibition using fluorogenic vivid substrates. AAPS Pharm. Sci., 2003, 5(2), E18.
115. Marks, B.D.; Smith, R.W.; Braun, H.A.; Goossens, T.A.; Christenson, M.; Ozers, M.S.; Lebakken, C.S.; Trubetskoy, O.V. A high throughput screening assay to screen for CYP2E1 metabolism and inhibition using a fluorogenic vivid p450 substrate. Assay Drug Dev. Technol., 2002, 1(1 Pt 1), 73-81.
116. O'Donnell, C.J.; Grime, K.; Courtney, P.; Slee, D.; Riley, R.J. The development of a cocktail CYP2B6, CYP2C8, and CYP3A5 inhibition assay and a preliminary assessment of utility in a drug discovery setting. Drug Metab. Dispos., 2007, 35(3), 381-385.
117. van de Waterbeemd, H. and E. Gifford, ADMET in silico modelling: towards prediction paradise? Nat. Rev. Drug Discov., 2003. 2(3), 192-204.
118. Gleeson, M.P.; Davis, A.M.; Chohan, K.K.; Paine, S.W.; Boyer, S.; Gavaghan, C.L.; Arnby, C.H.; Kankkonen, C.; Albertson, N. Generation of in-silico cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A4 inhibition QSAR models. J. Comput. Aided Mol. Des., 2007, 21(10-11), 559-573.
119. Kenworthy, K.E.; Bloomer, J.C.; Clarke, S.E.; Houston, J.B. CYP3A4 drug interactions: correlation of 10 in vitro probe substrates. Br. J. Clin. Pharmacol., 1999, 48(5), 716-727.
120. Korzekwa, K.R.; Krishnamachary, N.; Shou, M.; Ogai, A.; Parise, R.A.; Rettie, A.E.; Gonzalez, F.J.; Tracy, T.S. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry, 1998, 37(12), 4137-4147.
121. Shou, M.; Mei, Q.; Ettore, M.W.; Jr., Dai, R.; Baillie, T.A.; Rushmore, T.H. Sigmoidal kinetic model for two co-operative substrate-binding sites in a cytochrome P450 3A4 active site: an example of the metabolism of diazepam and its derivatives. Biochem. J., 1999, 340(Pt 3), 845-853.
122. Yoon, M.Y.; Campbell, A.P.; Atkins, W.M. "Allosterism" in the elementary steps of the cytochrome P450 reaction cycle. Drug Metab. Rev., 2004, 36(2), 219-230.
123. Mao, B.; Gozalbes, R.; Barbosa, F.; Migeon, J.; Merrick, S.; Kamm, K.; Wong, E.; Costales, C.; Shi, W.; Wu, C.; Froloff, N. QSAR modeling of in vitro inhibition of cytochrome P450 3A4. J. Chem. Inf. Model, 2006, 46(5), 2125-2134.
124. McMasters, D.R.; Torres, R.A.; Crathern, S.J.; Dooney, D.L.; Nachbar, R.B.; Sheridan, R.P.; Korzekwa, K.R. Inhibition of recombinant cytochrome P450 isoforms 2D6 and 2C9 by diverse drug-like molecules. J. Med. Chem., 2007, 50(14), 3205-3213.
125. Eitrich, T.; Kless, A.; Druska, C.; Meyer, W.; Grotendorst, J. Classification of highly unbalanced CYP450 data of drugs using cost sensitive machine learning techniques. J. Chem. Inf. Model, 2007, 47(1), 92-103.
126. O'Brien, S.E.; de Groot, M.J. Greater than the sum of its parts: combining models for useful ADMET prediction. J. Med. Chem., 2005, 48(4), 1287-1291.
127. Arimoto, R.; Prasad, M.A.; Gifford, E.M. Development of CYP3A4 inhibition models: comparisons of machine-learning techniques and molecular descriptors. J. Biomol. Screen., 2005, 10(3), 197-205.
128. Hudelson, M.G.; Jones, J.P. Line-walking method for predicting the inhibition of P450 drug metabolism. J. Med. Chem., 2006, 49(14), 4367-4373.
129. Ekins, S.; Bravi, G.; Binkley, S.; Gillespie, J.S.; Ring, B.J.; Wikel, J.H.; Wrighton, S.A. Three- and four-dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2C9 inhibitors. Drug Metab. Dispos., 2000, 28(8), 94-1002.
130. Ekins, S.; Bravi, G.; Binkley, S.; Gillespie, J.S.; Ring, B.J.; Wikel, J.H.; Wrighton, S.A. Three and four dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2D6 inhibitors. Pharmacogenetics, 1999, 9(4), 477-489.
131. Ekins, S.; Bravi, G.; Binkley, S.; Gillespie, J.S.; Ring, B.J.; Wikel, J.H.; Wrighton, S.A. Three- and four-dimensional quantitative structure activity relationship analyses of cytochrome P-450 3A4 inhibitors. J. Pharmacol. Exp. Ther., 1999, 290(1), 429-438.
132. Sciabola, S.; Morao, I.; de Groot, M.J. Pharmacophoric fingerprint method (TOPP) for 3D-QSAR modeling: application to CYP2D6 metabolic stability. J. Chem. Inf. Model., 2007, 47(1), 76-84.
133. Rowland, P.; Blaney, F.E.; Smyth, M.G.; Jones, J.J.; Leydon, V.R.; Oxbrow, A.K.; Lewis, C.J.; Tennant, M.G.; Modi, S.; Eggleston, D.S.; Chenery, R.J.; Bridges, A.M. Crystal structure of human cytochrome P450 2D6. J. Biol. Chem., 2006, 281(11), 7614-7622.
134. Wester, M.R.; Yano, J.K.; Schoch, G.A.; Yang, C.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-A resolution. J. Biol. Chem., 2004, 279(34), 35630-35637.
135. Schoch, G.A.; Yano, J.K.; Wester, M.R.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J. Biol. Chem., 2004, 279(10), 9497-9503.
136. Yu, J.; Paine, M.J.; Marechal, J.D.; Kemp, C.A.; Ward, C.J.; Brown, S.; Sutcliffe, M.J.; Roberts, G.C.; Rankin, E.M.; Wolf, C.R. In silico prediction of drug binding to CYP2D6: identification of a new metabolite of metoclopramide. Drug Metab. Dispos., 2006, 34(8), 1386-1392.
137. Shin, J.G.; Soukhova, N.; Flockhart, D.A. Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab. Dispos., 1999, 27(9), 1078-1084.
138. Karam, W.G.; Goldstein, J.A.; Lasker, J.M.; Ghanayem, B.I.. Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. Drug Metab. Dispos., 1996, 24(10), 1081-1087.
139. Foti, R.S.; Wahlstrom, J.L.; Wienkers, L.C. The in vitro drug interaction potential of dietary supplements containing multiple herbal components. Drug Metab. Dispos., 2007, 35(2), 185-188.
140. Marks, B.D.; Thompson, D.; Volak, L.; Zlokarnik, G.; Trubetskoy, O.V. Characterization of In vitro HTS Assays with Vivid Fluorogenic Substrates and Recombinant Human CYP1A2, 2D6, 2C9, 2C19 and 3A4. Drug Discovery and Development of Innovative Therapeutics, Boston, MA, 2004.