Comparison of metabolic soft spot predictions of CYP3A4, CYP2C9 and CYP2D6 substrates using MetaSite and starDrop

Combinatorial Chemistry and High Throughput Screening

Volumn 14, Issue 9, 2011, Pages 811-823

  Shin, Young G ^a   Le, Hoa ^a   Khojasteh, Cyrus ^a   Hop, Cornelis E C A ^a  

^a GENENTECH INC   (United States)

Author keywords

CYP2C9; CYP2D6; CYP3A4; MetaSite; Site of metabolism prediction; StarDrop

Indexed keywords

1 (2 BROMO 4,5 DIMETHOXYBENZYL) 1,2,3,4 TETRAHYDRO 7 HYDROXY 6 METHOXY 2 METHYLISOQUINOLINE; AFLATOXIN; AMITRIPTYLINE; BUFURALOL; CODEINE; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DEBRISOQUINE; DESIPRAMINE; DEXTROMETHORPHAN; DICLOFENAC; ERYTHROMYCIN; ETHINYLESTRADIOL; ETOPOSIDE; FLURBIPROFEN; IMIPRAMINE; LORNOXICAM; MEFENAMIC ACID; METOPROLOL; MIDAZOLAM; NAPROXEN; NIFEDIPINE; PHENACETIN; PROGESTERONE; PROPRANOLOL; TAMOXIFEN; TESTOSTERONE; UNINDEXED DRUG; VERAPAMIL;

ARTICLE; DRUG METABOLISM; HUMAN; HUMAN CELL; LIVER MICROSOME; METABOLITE; PRIORITY JOURNAL;

ARYL HYDROCARBON HYDROXYLASES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; HUMANS; MICROSOMES, LIVER; SPECTROPHOTOMETRY, ULTRAVIOLET; SUBSTRATE SPECIFICITY; TANDEM MASS SPECTROMETRY;

EID: 80052464427     PISSN: 13862073     EISSN: 18755402     Source Type: Journal    
DOI: 10.2174/138620711796957170     Document Type: Article

References (25)

1. Bertz, R. J.; Granneman, G. R. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin. Pharmacokinet., 1997, 32, 210-258. (Pubitemid 27122521)
2. Kennedy, T. Managing the drug discovery/development interface. Drug Discov. Today, 1997, 2, 436-444. (Pubitemid 27387353)
3. Carlson, T. J.; Fisher, M. B. Recent advances in high throughput screening for ADME properties. Comb. Chem. High Throughput Screen., 2008, 11, 258-264. (Pubitemid 351480898)
4. Testa, B.; Balmat, A. L.; Long, A. Predicting drug metabolism: concepts and challenges. Pure Appl. Chem., 2004, 76, 907-914.
5. Testa, B.; Balmat, A. L.; Long, A.; Judson, P. Predicting drug metabolism-an evaluation of the expert system METEOR. Chem. Biodivers., 2005, 2, 872-885. (Pubitemid 41064996)
6. Borodina, Y.; Rudik, A.; Filimonov, D.; Kharchevnikova, N.; Dmitriev, A.; Blinova, V.; Poroikov, V. A new statistical approach to predicting aromatic hydroxylation sites. Comparison with model-based approaches. J. Chem. Inf. Comput. Sci., 2004, 44, 1998-2009.
7. Sheridan, R. P.; Korzekwa, K. R.; Torres, R. A.; Walker, M. J. Empirical regioselectivity models for human cytochrome P450 3A4, 2D6, and 2C9. J. Med. Chem., 2007, 50, 3173-3184. (Pubitemid 47065966)
8. Jones, J. P.; Mysinger, M.; KOrzekwa, K.R. Computational models for cytochrome P450: a predictive electronic model for aromatic oxidation and hydrogen atom abstraction. Drug Metab. Dispos., 2002, 30, 7-12. (Pubitemid 34016934)
9. Hines, R. N.; Luo, Z.; Cresteil, T.; Ding, X.; Prough, R. A.; Fitzpatrick, J. L.; Ripp, S. L.; Falkner, K. C.; Ge, N.-L.; Levine, A.; Elferink, C. J. Molecular regulation of genes encoding xenobioticmetabolizing enzymes: mechanisms involving endogenous factors. Drug Metab. Dispos., 2001, 29, 623-633. (Pubitemid 32374561)
10. Segall, M. D.; Payne, M. C.; Ellis, S. W.; Tucker, G. T.; Eddershaw, P. J. First principles investigation of singly reduced cytochrome P450. Xenobiotica, 1999, 29, 561-571. (Pubitemid 29332741)
11. Afzelius, L.; Zamora, I.; Misimirembwa, C. M.; Karlen, A.; Andersson, T. B.; Mecucci, S.; Baroni, M.; Cruciani, G. Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors. J. Med. Chem., 2004, 47, 907-914. (Pubitemid 38176793)
12. 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. (Pubitemid 36637916)
13. Korzekwa, K. R.; Jones, J. P.; Gilette, J. R. Theoretical studies on cytochrome P-450 mediated hydroxylation: A predictive model for hydrogen atom abstractions. J. Am. Chem. Soc., 1990, 112, 7042- 7046. (Pubitemid 20319136)
14. Jones, J. P.; Mysinger, M.; Korzekwa, K. R. Computational models for cytochrome P450: A predictive electronic model for aromatic oxidation and hydrogen atom abstraction. Drug Metab. Dispos., 2002, 30, 7-12. (Pubitemid 34016934)
15. Singh, 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)
16. de Groot, M. J.; Ackland, M. J.; Horne, 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. (Pubitemid 29483023)
17. Zamora, I.; Afzelius, L.; Cruciani, G. Predicting drug metabolism: a site of metabolism prediction tool applied to the chtochrome P450 2C9. J. Med. Chem., 2003, 46, 2313-2324. (Pubitemid 36637916)
18. Cruciani, G.; Carosati, E.; Boeck, B. D.; Ethirajulu, K.; Mackie, C.; Howe, T.; Vianello, R. MetaSite: Understanding metabolism in human cytochromes from the perspective of the chemist. J. Med Chem., 2005, 48, 6970-6979. (Pubitemid 41533118)
19. Rydberg, P.; Gloriam, D. E.; Zaretzki, J.; Breneman, C.; Olsen, L. SMARTCyp: A 2D method for prediction of cytochrome P450- mediated drug metabolism. ACS Med. Chem. Lett., 2010, 1, 96- 100.
20. Trunzer, M.; Faller, B.; Zimmerlin, A. Metabolic soft spot identification and compound optimization in early discovery phase using MetaSite and LC-MS/MS validation, J. Med. Chem., 2009, 52, 329-335.
21. Segall, M.; Champness, E.; Obrezanova, O.; Leeding, C. Beyond profiling: Using ADMET models to guide decisions. Chemistry & Biodiversity, 2009, 6, 2144-2151.
22. Halladay, JS.; Wong, S.; Jaffer, SM.; Sinhababu, AK.; Khojasteh-Bakht, SC. Metabolic stability screen for drug discovery using cassette analysis and column switching. Drug Metab Lett., 2007, 1, 67-72.
23. Caron, G.; Ermondi, G.; Testa, B. Predicting the oxidative metabolism of statins: An application of the MetaSite algorithm. Pharm. Res., 2007, 24, 480-501. (Pubitemid 46295168)
24. Zhou, D. S.; Afzelius, L.; Grimm, S. W.; Andersson, T. B.; Zauhar, R. J.; Zamora, I. Comparison of methods for the prediction of the metabolic sites for CYP3A4-mediated metabolic reactions. Drug Metab. Dispos., 2006, 34, 976-983. (Pubitemid 43763754)
25. Lewis, D. Human Cytochrome P450 associated with the phase 1 metabolism of drugs and other xenobiotics: A compilation of substrates and inhibitors of the CYP1, CYP2 and CYP3 families. Curr. Med. Chem., 2003, 10, 1955-1972. (Pubitemid 37139057)