High throughput P450 inhibition screens in early drug discovery

Drug Discovery Today

Volumn 10, Issue 21, 2005, Pages 1443-1450

  Zlokarnik, Gregor ^a   Grootenhuis, Peter D J ^a   Watson, John B ^b  

^a VERTEX PHARMACEUTICALS   (United States)

^b PROMEGA CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLOPURINOL; AMIODARONE; CIMETIDINE; CIPROFLOXACIN; CLARITHROMYCIN; CYTOCHROME P450; DANAZOL; DILTIAZEM; DISULFIRAM; ERYTHROMYCIN; FLUCONAZOLE; FLUVOXAMINE; INDINAVIR; KETOCONAZOLE; MIBEFRADIL; MICONAZOLE; MIFEPRISTONE; NEFAZODONE; NELFINAVIR; NICARDIPINE; NORFLOXACIN; RITONAVIR; SAQUINAVIR; VERAPAMIL;

CALIBRATION; DRUG MARKETING; DRUG POTENCY; ENZYME INHIBITION; FLUORESCENCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIGH THROUGHPUT SCREENING; HUMAN; LUMINESCENCE; NONHUMAN; RADIOACTIVITY; REVIEW;

CALIBRATION; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; DRUG INTERACTIONS;

EID: 26944495704     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1359-6446(05)03580-4     Document Type: Review

References (73)

1. Lin J. The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery Curr. Top. Med. Chem. 3 2003 1125 1154
2. van de Waterbeemd H. High-throughput and in silico techniques in drug metabolism and pharmacokinetics Curr. Opin. Drug Discov. Devel. 5 2002 33 43
3. Riley R.J., Grime K. Metabolic screening in vitro: metabolic stability, CYP inhibition and induction Drug Discov. Today: Technol. 1 2004 365 372
4. Riley R.J., Kenna J.G. Cellular models for ADMET predictions and evaluation of drug-drug interactions Curr. Opin. Drug Discov. Devel. 7 2004 86 99
5. Riley R.J. The potential pharmacological and toxicological impact of P450 screening Curr. Opin. Drug Discov. Devel. 4 2001 45 54
6. Kariv I. Improvement of 'hit-to-lead' optimization by integration of in vitro HTS experimental models for early determination of pharmacokinetic properties Comb. Chem. High Throughput Screen 5 2002 459 472
7. Bjornsson T.D. The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective Drug Metab. Dispos. 31 2003 815 832
8. Dresser G.K., Bailey D.G. A basic conceptual and practical overview of interactions with highly prescribed drugs Can. J. Clin. Pharmacol. 9 2002 191 198
9. Sedman A.J. Cimetidine-drug interactions Am. J. Med. 76 1984 109 114
10. Welker H.A. Clinical pharmacokinetics of mibefradil Clin. Pharmacokinet. 35 1998 405 423
11. Riley R.J. Development of a generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery Pharm. Res. 18 2001 652 655
12. Rogerson T.D. Steric factors in the inhibitory interaction of imidazoles with microsomal enzymes Biochem. Pharmacol. 26 1977 1039 1042
13. Racha J.K. Mechanism-based inactivation of human cytochrome P450 1A2 by furafylline: detection of a 1:1 adduct to protein and evidence for the formation of a novel imidazomethide intermediate Biochemistry 37 1998 7407 7419
14. Lin J.H., Lu A.Y. Inhibition and induction of cytochrome P450 and the clinical implications Clin. Pharmacokinet. 35 1998 361 390
15. Walsky R.L. Examination of 209 drugs for inhibition of cytochrome P450 2C8 J. Clin. Pharmacol. 45 2005 68 78
16. Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data Drug Metab. Rev. 34 2002 83 448
17. Nelson D.R. Introductory remarks on human CYPs Drug Metab. Rev. 34 2002 1 5
18. Burbaum J.J. Miniaturization technologies in HTS: how fast, how small, how soon? Drug Discov Today 3 1998 313 322
19. Dunn D.A., Feygin I. Challenges and solutions to ultra-high-throughput screening assay miniaturization: submicroliter fluid handling Drug Discov. Today 5 Suppl. 1 2000 84 91
20. Wölcke J., Ullmann D. Miniaturized HTS technologies - uHTS Drug Discov. Today 6 2001 637 646
21. Braun D. Mainstreaming microfluidics: diffusing microfluidics technology in the marketplace Pharmacogenomics 4 2003 375 378
22. Cheng X., Hochlowski J. Current application of mass spectrometry to combinatorial chemistry Anal. Chem. 74 2002 2679 2690
23. Ackermann B.L. Recent advances in use of LC/MS/MS for quantitative high-throughput bioanalytical support of drug discovery Curr. Top. Med. Chem. 2 2002 53 66
24. Di L. Optimization of a higher throughput microsomal stability screening assay for profiling drug discovery candidates J. Biomol. Screen 8 2003 453 462
25. Masimirembwa C.M. In vitro high throughput screening of compounds for favorable metabolic properties in drug discovery Comb. Chem. High Throughput Screen 4 2001 245 263
26. Ansede J.H., Thakker D.R. High-throughput screening for stability and inhibitory activity of compounds toward cytochrome P450-mediated metabolism J. Pharm. Sci. 93 2004 239 255
27. Dierks E.A. 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. 29 2001 23 29
28. Weaver R. Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation Drug Metab. Dispos. 31 2003 955 966
29. Rodrigues A.D. Measurement of liver microsomal cytochrome p450 (CYP2D6) activity using [O-methyl-14C]dextromethorphan Anal. Biochem. 219 1994 309 320
30. Moody G.C. Fully automated analysis of activities catalyzed by the major human liver cytochrome P450 (CYP) enzymes: assessment of human CYP inhibition potential Xenobiotica 29 1999 53 75
31. Delaporte E. The potential for CYP2D6 inhibition screening using a novel scintillation proximity assay-based approach J. Biomol. Screen 6 2001 225 231
32. Clarke S.E. In vitro assessment of human cytochrome P450 Xenobiotica 28 1998 1167 1202
33. Miller V.P. Fluorometric high-throughput screening for inhibitors of cytochrome P450 Ann. N. Y. Acad. Sci. 919 2000 26 32
34. Chougnet A. Design and synthesis of a new fluorescent probe for cytochrome P450 3A4 (CYP 3A4) Bioorg. Med. Chem. Lett. 13 2003 3643 3645
35. Zhang R. Design, synthesis and evaluation of novel P450 fluorescent probes bearing a-cyanoether Tetrahedron Lett. 44 2003 4331 4334
36. Bapiro T.E. Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s Drug Metab. Dispos. 29 2001 30 35
37. Kariv I. Development of a miniaturized 384-well high throughput screen for the detection of substrates of cytochrome P450 2D6 and 3A4 metabolism J. Biomol. Screen 6 2001 91 99
38. Makings, L.R. and Zlokarnik, G. (2000) Optical molecular sensors for cytochrome P450 activity. USP6143492 Aurora Biosciences Corp
39. Trubetskoy O.V. Highly miniaturized formats for in vitro drug metabolism assays using vivid fluorescent substrates and recombinant human cytochrome P450 enzymes J. Biomol. Screen 10 2005 56 66
40. Cohen L.H. In vitro drug interactions of cytochrome P450: An evaluation of fluorogenic to conventional substrates Drug Metab. Dispos. 31 2003 1005 1015
41. Cali, J.J. et al. (2004) Luminescence-based methods and probes for measuring cytochrome P450 activity. USP application 20040171099 Promega Corp
42. de Groot M.J. In silico methods for predicting ligand binding determinants of cytochromes P450 Curr. Top. Med. Chem. 4 2004 1803 1824
43. de Graaf C. Cytochrome P450 in silico: an integrative modeling approach J. Med. Chem. 48 2005 2725 2755
44. Clark D.E., Grootenhuis P.D.J. Progress in computational methods for the prediction of ADMET properties Curr. Opin. Drug Discov. Devel. 5 2002 382 390
45. Ekins S. Generation and validation of rapid computational filters for CYP2D6 and CYP3A4 Drug Metab. Dispos. 31 2003 1077 1080
46. Molnar L., Keseru G.M. A neural network based virtual screening of cytochrome P450 3A4 inhibitors Bioorg. Med. Chem. Lett. 12 2002 419 421
47. O'Brien S.E., de Groot M.J. Greater than the sum of its parts: combining models for useful ADMET prediction J. Med. Chem. 48 2005 1287 1291
48. Balakin K.V. Kohonen maps for prediction of binding to human cytochrome P450 3A4 Drug Metab. Dispos. 32 2004 1183 1189
49. Le Bourdonnec B. Arylacetamide kappa opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity Bioorg. Med. Chem. Lett. 15 2005 2647 2652
50. Williams P.A. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone Science 305 2004 683 686
51. Yano J.K. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution J. Biol. Chem. 279 2004 38091 38094
52. Williams P.A. Crystal structure of human cytochrome P450 2C9 with bound warfarin Nature 424 2003 464 468
53. Kirton S.B. Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins Proteins 58 2005 836 844
54. Hutzler M. Predicting drug-drug interactions in drug discovery: where are we now and where are we going? Curr Opin. Drug Discov. Devel. 8 2005 51 58
55. Nomeir A.A. Inhibition of CYP3A4 in a rapid microtiter plate assay using recombinant enzyme and in human liver microsomes using conventional substrates Drug Metab. Dispos. 29 2001 748 753
56. Kenworthy K.E. CYP3A4 drug interactions: correlation of 10 in vitro probe substrates Br. J. Clin. Pharmacol. 48 1999 716 727
57. Stresser D.M. Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates Drug Metab. Dispos. 28 2000 1440 1448
58. Thummel K.E., Wilkinson G.R. In vitro and in vivo drug interactions involving human CYP3A Annu. Rev. Pharmacol. Toxicol. 38 1998 389 430
59. Weaver R.J. Assessment of drug-drug interactions: concepts and approaches Xenobiotica 31 2001 499 538
60. Shimada T. Interindividual 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. 270 1994 414 423
61. Tran T.H. Microsomal protein concentration modifies the apparent inhibitory potency of CYP3A inhibitors Drug Metab. Dispos. 30 2002 1441 1445
62. Shou M. Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site Biochemistry 33 1994 6450 6455
63. Koley A.P. CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers J. Biol. Chem. 270 1995 5014 5018
64. Kenworthy K.E. Multisite kinetic models for CYP3A4: simultaneous activation and inhibition of diazepam and testosterone metabolism Drug Metab. Dispos. 29 2001 1644 1651
65. Schulz M., Schmoldt A. Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics Pharmazie 58 2003 447 474
66. Campana C. Clinically significant drug interactions with cyclosporin An update. Clin. Pharmacokinet. 30 1996 141 179
67. Michalets E.L. Update: clinically significant cytochrome P-450 drug interactions Pharmacotherapy 18 1998 84 112
68. Chaturvedi P.R. Prediction of pharmacokinetic properties using experimental approaches during early drug discovery Curr. Opin. Chem. Biol. 5 2001 452 463
69. Ito K. Database analyses for the prediction of in vivo drug-drug interactions from in vitro data Br. J. Clin. Pharmacol. 57 2004 473 486
70. von Moltke L.L. In vitro approaches to predicting drug interactions in vivo Biochem. Pharmacol. 55 1998 113 122
71. Venkatakrishnan K. Drug metabolism and drug interactions: application and clinical value of in vitro models Curr. Drug Metab. 4 2003 423 459
72. Zhou S. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs Clin. Pharmacokinet. 44 2005 279 304
73. Davis A.M., Riley R.J. Predictive ADMET studies, the challenges and the opportunities Curr. Opin. Chem. Biol. 8 2004 378 386