Novel application of 2D and 3D-similarity searches to identify substrates among cytochrome P450 2C9, 2D6, and 3A4

Journal of Chemical Information and Modeling

Volumn 50, Issue 1, 2010, Pages 97-109

  Freitas, R F ^a   Bauab, R L ^a   Montanari, C A ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYMES; SUBSTRATES;

DRUG-DRUG INTERACTIONS; FALSE POSITIVE RATES; GENETIC POLYMORPHISMS; MULTIPLE REFERENCES; NOVEL APPLICATIONS; SIMILARITY SEARCH; TRUE POSITIVE RATES; VALIDATION DATA;

DRUG INTERACTIONS;

CYTOCHROME P450; CYTOCHROME P450 2D6; CYTOCHROME P450 3A; ISOENZYME;

AREA UNDER THE CURVE; ARTICLE; DRUG DEVELOPMENT; METABOLISM; METHODOLOGY; PROTEIN BINDING; RECEIVER OPERATING CHARACTERISTIC; REPRODUCIBILITY;

AREA UNDER CURVE; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DISCOVERY; ISOENZYMES; PROTEIN BINDING; REPRODUCIBILITY OF RESULTS; ROC CURVE;

EID: 75749083658     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci900074t     Document Type: Article

References (37)

1. Nigsch, F.; Mitchell, J. B. O. How to winnow actives from inactives: introducing molecular orthogonal sparse bigrams (MOSBs) and multiclass winnow. J. Chem. Inf. Model. 2008, 48, 306-318.
2. Sheridan, R. P.; Kearsley, S. K. Why do we need so many chemical similarity search methods. Drug Discovery Today 2002, 7, 903-911.
3. (3) Willett, P. Similarity-based virtual screening using 2D fingerprints. Drug Discovery Today 2006, 11, 1046-1053. (Pubitemid 44792477)
4. (4)Kola,I.;Landis,J.Canthepharmaceuticalindustryreduceattritionrates.J. Med.Chem.2004,3,711-716.(Pubitemid39173511)
5. Tillement, J. P.; Tremblay, D. Clinical Pharmacokinetic Criteria for Drug Research. In Comprehensive Medicinal Chemistry II: ADMETox Approaches, 1st ed.; Triggle, D. J., Taylor, J. B., Eds.; Elsevier: Amsterdam, The Netherlands, 2006; Vol.5, pp 11-30.
6. Wienkers, L. C.; Heath, T. G. Predicting in vivo drug interactions from in vitro drug discovery data. Nat. Rev. Drug Discovery 2005, 4, 825-833.
7. (7) Lill, M. A.; Dobler, M.; Vedani, A. Prediction of small-molecule binding to cytochrome P450 3A4: Flexible docking combined with multidimensional QSAR. ChemMedChem 2006, 1, 73-81. (Pubitemid 44104980)
8. Iyer, R.; Zhang, D.; Zhang, D. Role of Drug Metabolism in Drug Development. In Drug Metabolism in Drug Design and Development: Basic Concepts and Practice, 1st ed.; Zhang, D., Zhu, M., Humphreys, W. G., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2008; Vol.1, pp 261-285.
9. Zamora, I.; Afzelius, L.; Cruciani, G. Predicting Drug Metabolism: A site of metabolism prediction tool applied to the cytochrome P450 2C9.J. Med. Chem. 2003, 46, 2313-2324.
10. de Groot, M. J.; Ackland, M. J.; Home, V. A.; Alex, A. A.; Jones, B. C. 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. 1999, 42, 4062-4070.
11. Bonn, B.; Masimirembwa, C. M.; Aristei, Y.; Zamora, I. The molecular basis of CYP2D6-mediated N-dealkylation: balance between metabolic clearance routes and enzyme inhibition. Drug Metab. Dispos. 2008, 36, 2199-2210.
12. Schuster, D.; Laggner, C.; Steindl, T. M.; Langer, T. Development and validation of an in silico P450 profiler based on pharmacophore models. Curr. Drug Discovery Technol. 2006, 3, 1-48.
13. (13) Sheridan, R. P.; Korzekwa, K. R.; Torres, R. A.; Walker, M. J. Empirical regioselectivity models for human cytochromes P450 3A4, 2D6, and 2C9. J. Med. Chem. 2007, 50, 3173-3184. (Pubitemid 47065966)
14. Ekins, S.; Bravi, G.; Wikel, J. H.; Wrighton, S. A. Three- dimensionalquantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J. Pharmacol. Exp. Ther. 1999, 291, 424-443.
15. (15) Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab. Rev. 2002, 34, 83-448. (Pubitemid 34311090)
16. (16) Terfloth, L.; Bienfait, B.; Gastaiger, J. Ligand-based models for the isoform specificity of cytochrome P450 3A4, 2D6, and 2C9 substrates. J. Chem. Inf. Model. 2007, 47, 1688-1701. (Pubitemid 47210071)
17. Yap, C. W.; Chen, Y. Z. Prediction of cytochrome P450 3A4, 2D6, and 2C9 inhibitors and substrates by using support vector machines. J. Chem. Inf. Model. 2005, 45, 982-992.
18. Schuffenhauer, A.; Floersheim, P.; Acklin, P.; Jacoby, E. Similarity metrics for ligands reflecting the similarity of the target proteins. J. Chem. Inf. Comput. Sci. 2003, 43, 391-405.
19. Pavlidis, P.; Nobel, W. S. Matrix2png: a utility for visualizing matrix data. Bioinformatics 2003, 19, 295-296.
20. Hawkins, P. C. D.; Warren, G. L.; Skillman, A. G.; Nicholls, A. How to do an evaluation: pitfalls and traps. J. Comput.-Aided Mol. Des. 2008, 22, 179-190.
21. Pham, T. A.; Jain, A. N. Parameter estimation for scoring proteinligand interactions using negative training data. J. Med. Chem. 2006, 49, 5856-5868.
22. (22) Sing, S. B.; Shen, L. Q.; Walker, M. J.; Sheridan, R. P. A model for predicting likely sites of CYP3A4-mediated metabolism on drug-like molecules. J. Med. Chem. 2003, 46, 1330-1336. (Pubitemid 36512698)
23. Kirchmair, J.; Ristic, S.; Eder, K.; Markt, P.; Wolber, G.; Laggner, C.; Langer, T. J. Fast and efficient in silico 3D screening: toward maximum computational efficiency of pharmacophore-based and shape-based approaches. J. Chem. Inf. Model. 2007, 47, 2182-2196.
24. (24) Maréchal, J. D.; Kemp, C. A.; Roberts, G. C. K.; Paine, M. J. I.; Wolf, C. R.; Sutcliffe, M. J. Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6-drug interactions. Br. J. Pharmacol. 2008, 153, S82-S89. (Pubitemid 351340994)
25. Groot, M. J.; Ackland, M. J.; Home, V. A.; Alex, A. A.; Jones, B. C. A novel approach to predicting P450 mediated drug metabolism. CUP2d6 catalyzed n-dealkylation reactions and qualitative metabolite predictions using a combined protein and pharmacophore model for CYP2D6. J. Med. Chem. 1999, 42, 4062-4070.
26. Moffat, K.; Gillet, V. J.; Whittle, M.; Bravi, G.; Leach, A. L. A comparison of field-based similarity searching methods: CatShape, FBSS, and ROCS. J. Chem. Inf. Model. 2008, 48, 719-729.
27. (27) Mcgaughey, G. B.; Sheridan, R. P.; Bayly, C. L.; Culberson, J. C.; Kreatsoulas, C.; Lindsley, S.; Maiorov, V.; Truchon, J. F.; Cornell, W. D. Comparison of topological, shape, and docking methods in virtual screening. J. Chem. Inf. Model. 2007, 47, 1504-1519. (Pubitemid 47210053)
28. (28) Kojej, T.; Engkvist, O.; Blomberg, N.; Muresan, S. Multifingerprint based similarity searches for targeted class compound selection. J. Chem. Inf. Model. 2006, 46, 1201-1213. (Pubitemid 43999164)
29. Hert, J.; Willett, P.; Wilton, D. J. Comparison of fingerprint-based methods for virtual screening using multiple bioactive reference structures. J. Chem. Inf. Comput. Sci. 2004, 44, 1177-1185.
30. (30) Hristozov, D. P.; Oprea, T. I.; Gasteiger, J. Virtual screening applications: a study of ligand-based methods and different structure representations in four different scenarios. J. Comput.-Aided Mol. Des. 2007, 21, 617-640. (Pubitemid 50003623)
31. Nicholls, A. What do we know and when do we know it. J. Comput.Aided Mol. Des. 2008, 22, 239-255.
32. Truchon, J. F.; Bayly, C. I. Evaluating virtual screening methods: good and bad metrics for the "early recognition" problem. J. Chem. Inf. Model. 2007, 47, 488-508.
33. de Graaf, C.; Oostenbrink, C.; Keizers, P. H. J.; Wijst, T.; Jongejan, A.; Vermeulen, N. P. E. Catalytic site prediction and virtual screening of Cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking. J. Med. Chem. 2006, 49, 2417-2430.
34. Cytochrome P450 Drug Interaction Table, http://medicine.iupui.edu/ clinpharm/ddis/table.asp; accessed June 10, 2009.
35. LigPrep, version 2.0; Schrödinger, LLC: New York, NY, 2005.
36. (36) Böstrom, J.; Greenwood, J. R.; Gottfries, J. Assessing the performance of omega with respect to retrieving bioactive conformations. J. Mol. Graphics Model. 2003, 21, 449-462. (Pubitemid 36120775)
37. SigmaPlot, version 10.0; Systat Software Inc.: San Jose, CA, 2008.