Designing better drugs: predicting cytochrome P450 metabolism

Drug Discovery Today

Volumn 11, Issue 13-14, 2006, Pages 601-606

  de Groot, Marcel J ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2A6; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DICLOFENAC; FLURBIPROFEN; XENOBIOTIC AGENT;

AMINO ACID SEQUENCE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME MECHANISM; ENZYME STRUCTURE; ENZYME SUBSTRATE; HUMAN; MODEL; NONHUMAN; PHARMACOPHORE; PREDICTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY; THREE DIMENSIONAL IMAGING;

BINDING SITES; COMPUTER SIMULATION; CRYSTALLIZATION; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DESIGN; ISOENZYMES; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33745216665     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2006.05.001     Document Type: Review

References (65)

1. Nelson D.R., et al. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 12 (1993) 1-51
2. Nelson D.R., et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6 (1996) 1-42
3. Smith D.A., and Jones B.C. Speculations on the substrate structure-activity relationship (SSAR) of cytochrome P450 enzymes. Biochem. Pharmacol. 44 (1992) 2089-2098
4. de Groot M.J., et al. In silico methods for predicting ligand binding determinants of cytochromes P450. Curr. Top. Med. Chem. 4 (2004) 1803-1824
5. Wrighton S.A., and Stevens J.C. The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol. 22 (1992) 1-21
6. Todeschini R., and Consonni V. Handbook of Molecular Descriptors (2000), Wiley-VCH
7. de Groot M.J., et al. In silico methods for predicting ligand binding determinants of cytochromes P450. Frontiers in Medicinal Chemistry Vol. 3 (2006), Bentham Science Publishers pp. 615-52
8. Gillam E.M.J. Opposites attract, or do they? Rethinking the P450 2D6 pharmacophore model. Trends Pharm. Sci. 23 (2002) 501
9. Modi S., et al. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase. Biochemistry 36 (1997) 4461-4470
10. Chothia C., and Lesk A.M. The relation between the divergence of sequence and structure in proteins. EMBO J. 5 (1986) 823-826
11. de Groot M.J., et al. Development of a combined protein and pharmacophore model for CYP2C9. J. Med. Chem. 45 (2002) 1983-1993
12. Williams P.A., et al. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424 (2003) 464-468
13. Wester M.R., et al. The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-Å resolution. J. Biol. Chem. 279 (2004) 35630-35637
14. Kirton S.B., et al. Comparative modelling of cytochromes P450. Adv. Drug Deliv. Rev. 54 (2002) 385-406
15. Williams P.A., et al. Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity. Mol. Cell 5 (2000) 121-131
16. Wester M.R., et al. Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 Å resolution: evidence for an induced fit model of substrate binding. Biochemistry 42 (2003) 9335-9345
17. Wester M.R., et al. Structure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 Å resolution: evidence for multiple substrate binding modes. Biochemistry 42 (2003) 6370-6379
18. Scott E.E., et al. An open conformation of mammalian cytochrome P450 2B4 at 1.6-Å resolution. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 13196-13201
19. Scott E.E., et al. Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-Å resolution. J. Biol. Chem. 279 (2004) 27294-27301
20. Zhao Y., et al. Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction. J. Biol. Chem. 281 (2006) 5973-5981
21. Rowland P., et al. Crystal structure of human cytochrome P450 2D6. J. Biol. Chem. 281 (2006) 7614-7622
22. Williams P.A., et al. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 305 (2004) 683-686
23. Yano J.K., et al. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-Å resolution. J. Biol. Chem. 279 (2004) 38091-38104
24. Wang Q., and Halpert J.R. Combined three-dimensional quantitative structure-activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling. Drug Metab. Dispos. 30 (2002) 86-95
25. Jones J.P., et al. Three-dimensional quantitative structure-activity relationship for inhibitors of cytochrome P4502C9. Drug Metab. Dispos. 24 (1996) 1-6
26. Rao S., et al. A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions. J. Med. Chem. 43 (2000) 2789-2796
27. Ridderström M., et al. Arginines 97 and 108 in CYP2C9 are important determinants of the catalytic function. Biochem. Biophys. Res. Commun. 270 (2000) 983-987
28. Afzelius L., et al. Competitive CYP2C9 inhibitors: enzyme inhibition studies, protein homology modeling, and three-dimensional quantitative structure-activity relationship analysis. Mol. Pharmacol. 59 (2001) 909-919
29. de Groot M.J., et al. Novel approach to predicting P450 mediated drug metabolism. The development of a combined protein and pharmacophore model for CYP2D6. J. Med. Chem. 42 (1999) 1515-1524
30. de Groot M.J., et al. A novel approach to predicting P450 mediated drug metabolism. CYP2D6 catalyzed N-dealkylation reactions and qualitative metabolite predictions using a combined protein and pharmacophore model for CYP2D6. J. Med. Chem. 42 (1999) 4062-4070
31. Schoch G.A., et al. Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J. Biol. Chem. 279 (2004) 9497-9503
32. Yano J.K., et al. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxalen. Nat. Struct. Mol. Biol. 12 (2005) 822-823
33. Strickler M., et al. Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101). Biochemistry 42 (2003) 11943-11950
34. Poulos T.L. Cytochrome P450 flexibility. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 13121-13122
35. Korzekwa K.R., et al. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 37 (1998) 4137-4147
36. Hosea N.A., et al. Elucidation of distinct ligand binding sites for cytochrome P450 3A4. Biochemistry 39 (2000) 5929-5939
37. Ekins S., et al. Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome P450 active sites. Drug Metab. Dispos. 29 (2001) 936-944
38. Ekins S., and Obach R.S. Three dimensional-quantitative structure activity relationship computational approaches for prediction of human in vitro intrinsic clearance. J. Pharmacol. Exp. Ther. 295 (2000) 463-473
39. O'Brien S.E., and de Groot M.J. Greater than the sum of its parts: combining models for useful ADMET prediction. J. Med. Chem. 48 (2005) 1287-1291
40. Ehresmann B., et al. Surface-Integral QSPR models: local energy properties. J. Chem. Inf. Model. 45 (2005) 1053-1060
41. Sanz F., et al. MEPSIM: A computational package for analysis and comparison of molecular eletrostatic potentials. J. Comput. Aided Mol. Des. 7 (1993) 337-347
42. López de Briñaz E., et al. Pharmacophore development for the interaction of cytochrome P450 1A2 with its substrates and inhibitors. In: Gundertofte K., and Jørgensen F.S. (Eds). Molecular Modeling and Prediction of Bioactivity (2000), Kluwer Academic/Plenum Publishers 141-146
43. Boyer S., and Zamora I. New methods in predictive metabolism. J. Comput. Aided Mol. Des. 16 (2002) 403-413
44. Egnell A.-C., et al. Generation and evaluation of a CYP2C9 heteroactivation pharmacophore. J. Pharmacol. Exp. Ther. 307 (2003) 878-887
45. Snyder R., et al. Three-dimensional quantitative structure activity relationship for Cyp2d6 substrates. Quant. Struct. Act. Relat. 21 (2002) 357-368
46. Egnell A.-C., et al. Predictive models of CYP3A4 heteroactivation: in vitro-in vivo scaling and pharmacophore modeling. J. Pharmacol. Exp. Ther. 312 (2005) 926-937
47. Ekins S., et al. In vitro and pharmacophore insights into CYP3A enzymes. Trends Pharmacol. Sci. 24 (2003) 161-166
48. Tanaka T., et al. Characterization of the CYP3A4 active site by homology modeling. Chem. Pharm. Bull. (Tokyo) 52 (2004) 830-835
49. Podust L.M., et al. Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 3068-3073
50. Park S.Y., et al. Crystal structure of nitric oxide reductase from denitrifying fungus Fusarium oxysporum. Nat. Struct. Biol. 4 (1997) 827-832
51. Poulos T.L., et al. Crystal structure of substrate-free Pseudomonas putida cytochrome P-450. Biochemistry 25 (1986) 5314-5322
52. Yano J.K., et al. Crystal structure of a thermophylic cytochrome P450 from the Archaeon Sulfolobus solfataricus. J. Biol. Chem. 275 (2000) 31086-31092
53. Ravichandran K.G., et al. Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450s. Science 261 (1993) 731-736
54. sca-2 from Streptomyces carbophilus involved in production of pravastatin sodium, a tissue-selective inhibitor of HMG-CoA reductase. Acta Crystallogr. D Biol. Crystallogr. 55 (1999) 1209-1211
55. Cupp-Vickery J., et al. Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity. Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 3050-3055
56. terp at 2.3 Å resolution. J. Mol. Biol. 236 (1994) 1169-1185
57. Leys D., et al. Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450. J. Biol. Chem. 278 (2003) 5141-5147
58. Lee D.S., et al. Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis. Crystallographic, spectroscopic, and mutational studies. J. Biol. Chem. 278 (2003) 9761-9767
59. Podust L.M., et al. Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways. Protein Sci. 13 (2004) 255-268
60. Podust L.M., et al. The 1.92-Å structure of Streptomyces coelicolor A3(2) CYP154C1. J. Biol. Chem. 278 (2003) 12214-12221
61. Zhao B., et al. Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2. J. Biol. Chem. 280 (2005) 11599-11607
62. Zerbe K., et al. Crystal structure of OxyB, a cytochrome P450 implicated in an oxidative phenol coupling reaction during vancomycin biosynthesis. J. Biol. Chem. 277 (2002) 47476-47485
63. Pylypenko O., et al. Crystal structure of OxyC, a cytochrome P450 implicated in an oxidative C-C coupling reaction during vancomycin biosynthesis. J. Biol. Chem. 278 (2003) 46727-46733
64. Nagano S., et al. Crystal structure of epothilone D-bound, epothilone B-bound and substrate-free forms of cytochrome P450epoK. J. Biol. Chem. 278 (2003) 44886-44893
65. Yano J.K., et al. Preliminary characterization and crystal structure of a thermostable cytochrome P450 from Thermus thermophilus. J. Biol. Chem. 278 (2003) 608-616