New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis

British Journal of Pharmacology

Volumn 150, Issue 7, 2007, Pages 932-942

  Korhonen, L E ^a   Turpeinen, M ^b   Rahnasto, M ^a   Wittekindt, C ^a   Poso, A ^a   Pelkonen, O ^b   Raunio, H ^a   Juvonen, R O ^a  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

^b UNIVERSITY OF OULU   (Finland)

Author keywords

4 (4 chlorobenzyl)pyridine; CoMFA; CYP2B6; Quantitative structure activity relationship

Indexed keywords

1 NAPHTHOL; 2 BENZYLANILINE; 2 INDANONE; 2 METHOXYNAPHTHALENE; 2 NAPHTHOL; 2,4 DIMETHYLQUINOLINE; 2,6 DIMETHYLQUINOLINE; 3 METHYLQUINOLINE; 4 (4 CHLOROBENZOYL)PYRIDINE; 4 (4 CHLOROBENZYL)PYRIDINE; 4 (4 NITROBENZYL)PYRIDINE; 4 BENZOYLPYRIDINE; 4 BENZYLPHENOL; 4 BENZYLPYRIDINE; 4 BROMOBENZALDEHYDE; 4 BROMOBENZYLBROMIDE; 4 CHLOROBENZOPHENONE; 4 HYDROXYBENZALDEHYDE; 4 HYDROXYBENZOPHENONE; 4,4 DIAMINODIPHENYLMETHANE; ANISALDEHYDE; BROMODIPHENYLMETHANE; CYTOCHROME P450 2B6; CYTOCHROME P450 INHIBITOR; DECANOLACTONE; ETHYLAMINE; LACTONE DERIVATIVE; PROTOCATECHUALDEHYDE; QUINALDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPETITIVE INHIBITION; DRUG ACTIVITY; DRUG POTENCY; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN TISSUE; IC 50; IN VITRO SELECTION; METHODOLOGY; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

CYTOCHROME P-450 ENZYME SYSTEM; DNA, COMPLEMENTARY; ENZYME INHIBITORS; HUMANS; MICROSOMES, LIVER; MODELS, MOLECULAR; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34047233676     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/sj.bjp.0707173     Document Type: Article

References (24)

1. Äbelö A, Andersson TB, Antonsson M, Naudot AK, Skanberg I, Weidolf L (2000). Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 28: 966-972.
2. Cramer III RI, Patterson D, Bunce J (1988). Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110: 5959-5960.
3. de Graaf C, Vermeulen NP, Feenstra KA (2005). Cytochrome P450 in silico: an integrative modeling approach. J Med Chem 48: 2725-2755.
4. Ekins S, Bravi G, Ring BJ, Gillespie TA, Gillespie JS, Vandenbranden M et al. (1999). Three-dimensional quantitative structure activity relationship analyses of substrates for CYP2B6. J Pharmacol Exp Ther 288: 21-29.
5. Ekins S, Vandenbranden M, Ring BJ, Gillespie JS, Yang TJ, Gelboin HV et al. (1998). Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther 286: 1253-1259.
6. Ha-Duong NT, Dijols S, Macherey AC, Dansette PM, Mansuy D (2001). Inhibition by ticlopidine and its derivatives of human liver cytochrome P450. Mechanism-based inactivation of CYP 2C19 by ticlopidine. Adv Exp Med Biol 500: 145-148.
7. Heyn H, White RB, Stevens JC (1996). Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Drug Metab Dispos 24: 948-954.
8. Hutzler JM, Messing DM, Wienkers LC (2005). Predicting drug-drug interactions in drug discovery: where are we now and where are we going? Curr Opin Drug Discov Dev 8: 51-58.
9. Kent UM, Juschyshyn MI, Hollenberg PF (2001). Mechanism-based inactivators as probes of cytochrome P450 structure and function. Curr Drug Metab 2: 215-243.
10. Korhonen LE, Rahnasto M, Mahonen NJ, Wittekindt C, Poso A, Juvonen RO et al. (2005). Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem 48: 3808-3815.
11. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U et al. (2001). Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11: 399-415.
12. Lewis DF (2000). On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: towards the prediction of human P450 substrate specificity and metabolism. Biochem Pharmacol 60: 293-306.
13. Li XQ, Bjorkman A, Andersson TB, Ridderstrom M, Masimirembwa CM (2002). Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther 300: 399-407.
14. Mimura M, Baba T, Yamazaki H, Ohmori S, Inui Y, Gonzalez FJ et al. (1993). Characterization of cytochrome P-450 2B6 in human liver microsomes. Drug Metab Dispos 21: 1048-1056.
15. Pelkonen O, Raunio H (2005). In vitro screening of drug metabolism during drug development: can we trust the predictions? Expert Opin Drug Metab Toxicol 1: 49-59.
16. Rae JM, Soukhova NV, Flockhart DA, Desta Z (2002). Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug Metab Dispos 30: 525-530.
17. Rahnasto M, Raunio H, Poso A, Wittekindt C, Juvonen RO (2005). Quantitative structure-activity relationship analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme. J Med Chem 48: 440-449.
18. Richter T, Murdter TE, Heinkele G, Pleiss J, Tatzel S, Schwab M et al. (2004). Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine. J Pharmacol Exp Ther 308: 189-197.
19. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (1994). 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: 414-423.
20. Stresser DM, Kupfer D (1999). Monospecific antipeptide antibody to cytochrome P-450 2B6. Drug Metab Dispos 27: 517-525.
21. Taavitsainen P, Juvonen R, Pelkonen O (2001). In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine), and its nonamine analog, cyclopropylbenzene. Drug Metab Dispos 29: 217-222.
22. Turpeinen M, Nieminen R, Juntunen T, Taavitsainen P, Raunio H, Pelkonen O (2004). Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver microsomes in vitro. Drug Metab Dispos 32: 626-631.
23. Turpeinen M, Raunio H, Pelkonen O (2006). The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr Drug Metab 7: 705-714.
24. Wang Q, Halpert JR (2002). Combined three-dimensional quantitative structure-activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling. Drug Metab Dispos 30: 86-95.