Quantitative structure-activity relationships (QSARs) in CYP3A4 inhibitors: The importance of lipophilic character and hydrogen bonding

Journal of Enzyme Inhibition and Medicinal Chemistry

Volumn 21, Issue 2, 2006, Pages 127-132

  Lewis, David F V ^a   Lake, Brian G ^b   Dickins, Maurice ^c  

^a UNIVERSITY OF SURREY   (United Kingdom)

^b BIBRA INTERNATIONAL   (United Kingdom)

^c PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

CYP3A4; Inhibition; Partition coefficient; QSAR; Statins

Indexed keywords

ASTEMIZOLE; ATORVASTATIN; CERIVASTATIN; CISAPRIDE; CLOTRIMAZOLE; CYCLOSPORIN; CYTOCHROME P450 3A4; CYTOCHROME P450 3A4 INHIBITOR; CYTOCHROME P450 INHIBITOR; ECONAZOLE; ERYTHROMYCIN; FLUCONAZOLE; FLUINDOSTATIN; GLIPIZIDE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; KETOCONAZOLE; METYRAPONE; MEVINOLIN; MIBEFRADIL; MICONAZOLE; MIDAZOLAM; NICARDIPINE; NIFEDIPINE; NIMODIPINE; PRAVASTATIN; SIMVASTATIN; TERFENADINE; TROLEANDOMYCIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL;

ARTICLE; BINDING AFFINITY; COMPETITIVE INHIBITION; CORRELATION ANALYSIS; CORRELATION COEFFICIENT; DRUG PROTEIN BINDING; ENZYME INHIBITION; HUMAN; HYDROGEN BOND; IC 50; IONIZATION; LIPOPHILICITY; MOLECULAR MODEL; PARTITION COEFFICIENT; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; HUMANS; HYDROGEN BONDING; KINETICS; LIPIDS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS;

EID: 33746175746     PISSN: 14756366     EISSN: 14756374     Source Type: Journal    
DOI: 10.1080/14756360500532747     Document Type: Article

References (21)

1. Lewis, DFV. (1996) Cytochromes P450: Structure, function and mechanism. London: Taylor & Francis.
2. Lewis, DFV. (2001) Guide to cytochromes P450 structure and function. London: Taylor & Francis.
3. Lewis, DFV. (2004) 57 varieties: The human cytochromes P450 Pharmacogenomics, 5, pp. 305-318.
4. Rendic, S and DiCarlo, FJ. (1997) Human cytochrome P450 enzymes: A status report summarizing their reactions, substrate, inducers and inhibitors Drug Met Rev, 29, pp. 413-580.
5. Rendic, S. (2002) Summary of information on human CYP enzymes: Human P450 metabolism data Drug Met Rev, 34, pp. 83-448.
6. Lewis, DFV and Eddershaw, PJ and Goldfarb, PS and Tarbit, MH. (1996) Molecular modelling of CYP3A4 from an alignment with CYP102: Identification of key interactions between putative active site residues and CYP3A-specific chemicals Xenobiotica, 6, pp. 1067-1086.
7. Lewis, DFV and Lake, BG and Dickins, M and Goldfarb, PS. (2004) Homology modelling of CYP3A4 from the CYP2C5 crystallographic template: Analysis of typical CYP3A4 substrate interactions Xenobiotica, 34, pp. 549-569.
8. Lewis, DFV. (2004) Quantitative Structure-Activity relationships (QSARs) for substrates of human cytochromes P450 CYP2 family enzymes Tox in Vitro, 18, pp. 89-97.
9. Lewis, DFV and Jacobs, MN and Dickins, M. (2004) The importance of compound lipophilicity for substrate binding to human P450s involved in drug metabolism DDT, 9, pp. 530-537.
10. Lewis, DFV and Dickins, M. (2003) Baseline lipophilicity relationships in human cytochromes P450 associated with drug metabolism Drug Met Rev, 35, pp. 1-18.
11. Ishigami, M and Honda, T and Takasaki, W and Ikeda, T and Komai, T and Ito, K and Sugiyama, Y. (2001) A comparison of the effects of 3-hydroxy-3-methylgutaryl-coenzyme A (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro Drug Met Disp, 29, pp. 282-288.
12. Stresser, DM and Blanchard, AP and Turner, SD and Erve, JCL and Dandeneau, AA and Miller, VP and Crespi, CL. (2000) Substrate-dependent modulation of CYP3A4 catalytic activity: Analysis of 27 test compounds with four fluorometric substrates Drug Met Disp, 28, pp. 1440-1448.
13. Ekins, S and Stresser, DM and Williams, JA. (2003) In vitro and pharmacophore insights into CYP3A enzymes TIPS, 24, pp. 161-166.
14. Riley, RJ and Parker, AJ and Trigg, S and Manners, CN. (2001) Development of generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery Pharm Res, 18, pp. 652-655.
15. Hansch C, Leo A, Hoekman D. Exploring QSAR: Hydrophobic electronic and steric constants. Am Chem Soc 1995.
16. Ekins, S and Bravi, G and Binkley, S and Gillespie, JS and Ring, BJ and Wikel, JH and Wrighton, SA. (1999) Three-dimensional quantitative Structure-Activity relationship (3D-QSAR) analysis of inhibitors of CYP3A4 J Pharm Exp Ther, 290, pp. 429-438.
17. Yano, JK and Wester, MR and Schoch, GA and Giffin, KJ and Stout, CD and Johnson, EF. (2004) The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05Å resolution J Biol Chem, 279, pp. 38091-38094.
18. Williams, PA and Cosme, J and Vinkovic, DM and Ward, A and Angove, HC and Day, PJ and Vonrhein, C and Tickle, IJ and Jhoti, H. (2004) Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone Science, 305, pp. 683-686.
19. Cortes, A and Cascante, M and Cardenas, ML and Cornish-Bowden, A. (2001) Relationships between inhibition constants, inhibitor concentrations for 50% inhibition and types of inhibition: New ways of analyzing data Biochem J, 357, pp. 263-268.
20. Domanski, TL and Halpert, JR. (2001) Analysis of mammalian cytochrome P450 structure and function by site-directed mutagenesis Curr Drug Met, 2, pp. 117-137.
21. Atkins, WM. (2004) Implications of the allosteric kinetics of cytochrome P450s DDT, 9, pp. 478-484.