In silico prediction of cytochrome P450 inhibitors

Drug Development Research

Volumn 67, Issue 5, 2006, Pages 417-429

  Refsgaard, Hanne H F ^a   Jensen, Berith F ^a,b   Christensen, Inge Thøger ^a   Hagen, Nina ^a   Brockhoff, Per B ^b  

^a NOVO NORDISK A S   (Denmark)

^b TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

CYP1A2; CYP2C9; CYP2D6; CYP3A4; Metabolism

Indexed keywords

ACETANILIDE; BUFURALOL; CAFFEINE; CIPROFLOXACIN; CODEINE; CYCLOSPORIN A; CYTOCHROME P450 1A2; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 INHIBITOR; DEBRISOQUINE; DEXTROMETHORPHAN; DICLOFENAC; ERYTHROMYCIN; ETHOXYRESORUFIN; FELODIPINE; FLUINDOSTATIN; FLUVOXAMINE; FURAFYLLINE; METOPROLOL; MIDAZOLAM; NIFEDIPINE; PHENACETIN; SIMVASTATIN; TERFENADINE; TESTOSTERONE; THEOPHYLLINE; TOLBUTAMIDE; UNINDEXED DRUG;

ACCURACY; DRUG METABOLISM; ENZYME INHIBITION; ENZYME SUBSTRATE; MOLECULAR MODEL; REVIEW; RISK ASSESSMENT; SCREENING; STATISTICAL ANALYSIS;

EID: 33749015188     PISSN: 02724391     EISSN: 10982299     Source Type: Journal    
DOI: 10.1002/ddr.20108     Document Type: Review

References (74)

1. Afzelius L, Zamora I, Ridderström M, Andersson TB, Karlén A, Masimirembwa CM. 2001. Competitive CYP2C9 inhibitors: enzyme inhibition studies, protein homology modeling, and three-dimensional quantitative structure-activity relationship analysis. Mol Pharmacol 59:909-919.
2. Afzelius L, Zamora I, Masimirembwa CM, Karlén A, Andersson TB, Zamora I. 2002. Discriminant and quantitative PLS analysis of competitive CYP 2C9 inhibitors versus non-inhibitors using alignment independent GRIND descriptors. J Computer-Aided Mol Design 16:443-458.
3. Afzelius L, Zamora I, Masimirembwa CM, Karlén A, Andersson TB, Mecucci S, Baroni M, Cruciani G. 2004. Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors J Med Chem 47:907-914.
4. Arimoto R, Prasad MA, Gifford EM. 2005. Development of CYP3A4 inhibition models: comparisons of machine-learning techniques and molecular descriptors. J Biomol Screen 10:197-205.
5. Balakin K, Ekins S, Bugrim A, Ivanenkov YA, Korolev D, Nikolsky YV, Skorenko AV, Ivashchenko AA, Savchuk NP, Nikolskaya T. 2004a. Kohonen Maps for prediction of binding to human cytochrome P450 3A4. Drug Metab Dispos 32:1183-1189.
6. Balakin K, Ekins S, Bugrim A, Ivanenkov YA, Korolev D, Nikolsky YV, Ivashchenko AA, Savchuk NP, Nikolskaya T. 2004b. Qualitative structure-metabolism relationship modeling of metabolic N-nealkylation reaction rates. Drug Metab Dispos 32:1111-1120.
7. Baroni M, Clementi S, Cruciani G, Costantino G, Riganelli D. 1992. Predictive ability of regression models. Part II: selection of the best predictive PLS model. J Chemometr 6:347-356.
8. Baroni M, Costantino G, Cruciani G, Riganelli D, Valigi R, Clementi S. 1993. Generating optimal linear PLS estimators (GOLPE): an advanced chemometric tool for handling 3D-QSAR problems. Quant Struct-Act Relat 12:9-20.
9. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, Kumar G, McLeod J, Obach SR, Roberts S, Roe A, Shah A, Snikeris F, Sullivan JT, Tweedie D, Vega JM, Walsh J, Wrighton SA. 2003. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharm 43:443-469.
10. Chohan KK, Paine SW, Mistry J, Barton P, Davis AM. 2005. A rapid computational filter for cytochrome P4501A2 inhibition potential of compound libraries. J Med Chem 48:5154-5161.
11. Cohen LH, Remley MJ, Raunig D, Vaz AD. 2003. In vitro drug interactions of cytochrome p450: an evaluation of fluorogenic to conventional substrates. Drug Metab Dispos 31:1005-1015.
12. de Graaf C, Vermeulen NPE, Feenstra KA. 2005. Cytochrome P450 in silico: an integrative modeling approach. J Med Chem 48:2725-2755.
13. de Groot MJ, Kirton SB, Sutcliffe MJ. 2004. In silico methods for predicting ligand binding determinants of cytochrome P450. Curr Topics Med Chem 4:1803-1824.
14. Egnell A-C, Eriksson C, Albertson N, Houston B, Boyer S. 2003. Generation and evaluation of a CYP2C9 heteroactivation pharmcophore. J Pharmacol Exp Ther 307:878-887.
15. Ekins S, Wrighton SA. 2001. Application of in silico approaches to predicting drug-drug interactions. J Pharmacol Tox Methods 45:65-69.
16. Ekins S, Bravi G, Binkley S, Gillespie JS, Ring BJ, Wikel JH, Wrighton SA. 1999a. Three- and four-dimensional quantitative structure activity relationship analyses of cytochrome P-450 3A4 inhibitors. J Pharmacol Exp Ther 290:429-438.
17. Ekins S, Bravi G, Binkley S, Gillespie JS, Ring BJ, Wikel JH, Wrighton SA. 1999b. Three- and four dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2D6 inhibitors. Pharmacogenetics 9:477-489.
18. Ekins S, Bravi G, Binkley S, Gillespie, JS, Ring BJ, Wikel JH, Wrighton SA. 2000. Three- and four-dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2C9 inhibitors. Drug Metab Dispos 28:994-1002.
19. Ekins S, de Groot MJ, Jones JP. 2001. Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites. Drug Metab Dispos 29:936-944.
20. Ekins S, Berbaum J, Harrison RK. 2003. Generation and validation of rapid computational filters for CYP2D6 and CYP3A4. Drug Metab Dispos 31:1077-1080.
21. Endres CJ, Hsiao P, Chung FS, Unadkat JD. 2006. The role of transporters in drug interactions. Eur J Pharm Sci 27:501-517.
22. Engel T. 2003. In: Gasteiger J, Engel T. editors. Chemoinformatics. Wienheim: Wiley-VCH Verlag GmbH & Co, p 71-72.
23. Fielding AH, Bell JF. 1997. A review of methods for the assessment of prediction errors in conservation presence/absence models. Environ Conserv 24:38-49.
24. Fontana E, Dansette PM, Poli SM. 2005. Cytochrome P450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab 6:413-454.
25. Fuhr U, Strobl G, Manaut F, Andres E-M, Sörgel F, Lopez-de-Brinas E, Chu DTW, Pernet AG, Mahr G, Danz F, Staib H. 1993. Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isoform CYP1A2. Mol Pharmacol 43:191-199.
26. Gao H, Shanmugasundaram V, Lee P. 2002. Estimation of aqueous solubility of organic compounds with QSPR approach. Pharm Res 4:497-503.
27. Guyon I, Elisseeff A. 2003. An Introduction to variable and feature selection. J Mach Learn Res 3:1157-1182.
28. Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J. 1998. In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos 26:536-539.
29. Hastie T, Tibshirani R, Friedman J. 2001. The elements of statistical learning. 2nd ed. New York: Springer-Verlag, p 266-278.
30. Holland JH. 1975. Adaption in natural and artificial systems. Ann Arbor: University of Michigan Press.
31. Hosea NA, Miller GP, Guengerich FP. 2000. Elucidation of distinct ligand binding sites for cytochrome P450 3A4. Biochemistry 39:5929-5939.
32. Ito K, Brown HS, Houston JB. 2004. Database analyses for the prediction of in vivo drug-drug interactions from in vitro data. Br J Clin Pharmacol 57:473-486.
33. Jensen BF, Refsgaard HHF, Bro R, Brockhoff PB. 2005. Classification of membrane permeability of drug candidates: a methodological investigation. QSAR Comb Sci 24:449-457.
34. Jones JP, He M, Trager WF, Rettie AE. 1996. Three-dimensional quantitative structure-activity relationship for inhibitors of cytochrome P4502C9. Drug Metab Dispos 24:1-6.
35. Jónsdóttir SO, Jørgensen FS, Brunak S. 2005. Prediction methods and databases within chemoinformatics: emphasis on drugs and drug candidates. Bioinformatics 21:2145-2160.
36. Kemp CA, Flanagan JU, Eldik AJV, Maréchal J-D, Wolf CR, Roberts GCK, Paine MJI, Sutcliffe MJ. 2004. Validation of model of cytochrome P450 2D6: an in silico tool for predicting metabolism and inhibition. J Med Chem 47:5340-5346.
37. Korhonen LE, Rahnasto M, Mähönen NJ, Wittekindt C, Poso A, Juvonen RO, Hannu R. 2005. Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem 48:3808-3815.
38. Kriegl JM, Arnhold T, Beck B, Fox T. 2005a. Prediction of human cytochrome p450 inhibition using support vector machines. QSAR Comb Sci 24:491-502.
39. Kriegl JM, Eriksson L, Arnhold T, Beck B, Johansson E, Fox T. 2005b. Multivariate modeling of cytochrome P450 3A4 inhibition. Eur J Pharmaceut Sci 24:451-463.
40. Labute P. 2000. A widely applicable set of descriptors. J Mol Graphics Model 18:464-477.
41. Lee H, Yeom H, Kim YG, Yoon CN, Jin C, Choi JS, Kim B-R, Kim D-H. 1998. Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids. Biochem Pharmacol 55:1369-1375.
42. Leardi R, Boggia R, Terrile M. 1992. Genetic algorithms as a strategy for feature selection. J Chemometr 6:267-281.
43. Lewis DFV. 2000. On the recognition of mammalien microsomal cytochrome P450 substrates and their characteristics. Biochem Pharmacol 60:293-306.
44. Livingstone DJ. 2000. The characterization of chemical structures using molecular properties. A survey. J Chem Inf Comput Sci 40:195-209.
45. Lu P, Lin Y, Rodrigues AD, Rushmore TH, Baillie TA, Shou M. 2001. Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3A4. Drug Metab Dispos 29:1473-1479.
46. Merkwirth C, Mauser H, Schulz-Gasch T, Roche O, Stahl M, Lengauer T. 2004. Ensemble methods for classification in cheminformatics. J Chem Inf Sci 44:1971-1978.
47. Molnár L, Keserü GM. 2002. A neural network based virtual screening of cytochrome P450 3A4 inhibitors. Bioorg Med Chem Lett 12:419-421.
48. Moon T, Chi MH, Kim D-H, Yoon CN, Choi Y-S. 2000. Quantitative structure-activity relationships (QSAR) study of flavonoid derivates for inhibition of cytochrome P450 1A2. Quant Struct-Act Relat 19:257-263.
49. Nikolova N, Jaworska J. 2003. Approaches to measure chemical similarity. A review. QSAR Comb Sci 22:1006-1026.
50. Nørgaard L, Saudland A, Wagner J, Nielsen JP, Munck L, Engelsen SB. 2000. Interval partial least-squares regression (iPLS): a comparative chemometric study with an example from near-infrared spectroscopy. Appl Spectrsc 54:413-419.
51. O'Brian SE, de Groot MJ. 2005. Greater than the sum of its parts: combining models for useful ADMET prediction. J Med Chem 48:1287-1291.
52. Oprea TI, Gottfries J. 2001. Chemography: The art of navigating in chemical space. J Comb Chem 3:157-166.
53. Rao S, Aoyama R, Schrag M, Trager WF, Rettie A, Jones JP. 2000. A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions. J Med Chem 43:2789-2796.
54. Refsgaard HHF, Jensen BF, Brockhoff PB, Padkjaer SB, Guldbrandt M, Christensen MS. 2005. In silico prediction of membrane permeability from calculated molecular parameters. J Med Chem 48:805-811.
55. Reunanen J. 2003. Overfitting in making comparisons between variable selection methods. J Mach Learn Res 3:1371-1382.
56. Riley RJ, Parker AJ, Trigg S, Manners CN. 2001. Development of generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery. Pharm Res 18:652-655.
57. Rowland P, Blaney FE, Smyth MG, Jones JJ, Leydon VR, Oxbrow AK, Lewis CJ, Tennant MG, Modi S, Eggleston DS, Chenery RJ, Bridges AM. 2006. Crystal structure of human cytochrome P450 2D6. JBC 281:7614-7622.
58. Salt DW, Yildiz N, Livingstone DJ, Tinsley J. 1992. The use of artificial neural networks in QSAR. Pestic Sci 36:161-170.
59. Schoch GA, Yano JK, Wester MR, Griffin KJ, Stout CD, Johnson EF. 2004. Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J Biol Chem 279:9497-9503.
60. Smith DA, Ackland MJ, Jones BC. 1997. Properties of cytochrome P450 isoenzymes and their substrates. Part 2: Properties of cytochrome P450 substrates. DDT 2:479-486.
61. Strobl GR, von Kruedener S, Stoeckigt J, Guengerich FP, Wolff T. 1993. Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies. J Med Chem 36:1136-1145.
62. Susnow RG, Dixon SL. 2003. Use of robust classification techniques for the prediction of human cytochrome P450 2D6 inhibition. J Chem Inf Comput Sci 43:1308-1315.
63. Sutter JM, Kalivas JH. 1993. Comparison of forward selection, backward elimination, and generalized simulated annealing for variable selection. Microchem J 47:60-66.
64. Thummel KE, Wilkinson GR. 1998. In vitro and in vivo drug interactions involving human CYP3A. Ann Review Pharmacol Toxicol 38:389-430.
65. Walsky RL, Obach RS. 2004. Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647-660.
66. Wanchana S, Yamashita F, Hashida M. 2003. QSAR Analysis of the inhibition of recombinant CYP 3A4 activity by structurally diverse compounds using a genetic algorithm-combined partial least squares method. Pharmacol Res 20:1401-1408.
67. Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, Jhoti H. 2003. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424:464-468.
68. Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti H. 2004. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 305:683-686.
69. Wold S. 1978. Cross-validatory estimation of the number of components in factor and principal components models. Technometrics 20:397-405.
70. Wold S, Martens H, Wold H. 1983. The multivariate calibration problem in chemistry solved by the PLS method. In: Kågström B, Ruhe A, editors. Lecture notes in mathematics, Vol. 973. Berlin: Springer-Verlag, p 286-293.
71. Xue L. 2000. Molecular descriptors in chemoinformatics, computational combinatorial chemistry, and virtual screening. Comb Chem HTS 3:363-372.
72. Yano JK, Wester MR, Schoch GA, Griffin KJ, Stout CD, Johnson EF. 2004. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution. J Biol Chem 279:38091-38094.
73. Zlokarnik G, Grootenhuis PDJ, Watson JB. 2005. High throughput P450 inhibition screens in early drug discovery. DDT 10:1443-1450.
74. Zuegge J, Fechner U, Roche O, Parrott NJ, Engkvist O, Schneider G. 2002. A fast virtual screening filter for cytochrome P450 inhibition liability of compound libraries. Quant Struct-Act Relat 21:249-256.