Molecular modelling of the human glucocorticoid receptor (hGR) ligand-binding domain (LBD) by homology with the human estrogen receptor α (hERα) LBD: Quantitative structure-activity relationships within a series of CYP3A4 inducers where induction is mediated via hGR involvement

Journal of Steroid Biochemistry and Molecular Biology

Volumn 82, Issue 2-3, 2002, Pages 195-199

  Lewis, D F V ^a   Ogg, M S ^b   Goldfarb, P S ^a   Gibson, G G ^a  

^a UNIVERSITY OF SURREY   (United Kingdom)

^b CMR International   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

16ALPHA CYANOPREGNENOLONE; AMINO ACID; CARBAMAZEPINE; CYTHIOATE; CYTOCHROME; CYTOCHROME P450 3A4; DEXAMETHASONE; ENZYME INDUCING AGENT; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; GLUCOCORTICOID RECEPTOR; METYRAPONE; PHENOBARBITAL; PHENYLBUTAZONE; PHENYTOIN; RIFAMPICIN; SPIRONOLACTONE; SULFINPYRAZONE;

ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CORRELATION ANALYSIS; ENZYME INDUCTION; HUMAN; HYDROGEN BOND; LIGAND BINDING; MOLECULAR MODEL; PHYSICAL CHEMISTRY; PROTEIN DOMAIN; PROTEIN FOLDING; PROTEIN INDUCTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STRUCTURAL HOMOLOGY;

AMINO ACID SEQUENCE; BINDING SITES; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INDUCTION; ESTROGEN RECEPTOR ALPHA; HUMANS; HYDROGEN BONDING; LIGANDS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, TERTIARY; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RECEPTORS, ESTROGEN; RECEPTORS, GLUCOCORTICOID; SEQUENCE ALIGNMENT; STATISTICS;

EID: 18744367206     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-0760(02)00158-9     Document Type: Article

References (17)

1. Honkakoski P., Negishi M. Regulation of cytochrome P450 (CYP) genes by nuclear receptors. Biochem. J. 347:2000;331-337.
2. Guengerich F.P. Cytochrome P450 3A4: regulation and role in drug metabolism. Annu. Rev. Pharmacol. Toxicol. 39:1999;1-17.
3. Quattrochi L.S., Guzelian P.S. CYP3A regulation: from pharmacology to nuclear receptors. Drug Metab. Dispos. 29:2001;615-622.
4. Waxman D.J. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR and PPAR. Arch. Biochem. Biophys. 369:1999;11-23.
5. Pascussi J.M., Drocourt L., Fabre J.M., Maurel P., Vilarem M.J. Dexamethasone induces pregnane X receptor and retinoid X receptor-α expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol. Pharmacol. 58:2000;361-372.
6. Lewis D.F.V., Ioannides C., Parke D.V., Schulte-Hermann R. Quantitative structure-activity relationships in a series of endogenous and synthetic steroids exhibiting induction of CYP3A activity and hepatomegaly associated with increased DNA synthesis. J. Steroid Biochem. Mol. Biol. 74:2000;179-185.
7. Brzozowski A.M., Pike A.C.W., Dauter Z., Hubbard R.E., Bonn R., Engstrom O., Ohman L., Green G.L., Gustafsson J.A., Carlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 389:1997;753-758.
8. M.S. Ogg, In Vitro Assessment of the Regulation of the Human CYP3A4 Gene, Ph.D. Thesis, University of Surrey, School of Biomedical and Life Sciences, 1998.
9. Ogg M.S., Gray T.J., Gibson G.G. Development of an in vitro reporter gene assay to assess xenobiotic induction of the human CYP3A4 gene. Eur. J. Drug Metab. Pharmacokinet. 22:1997;311-313.
10. Ogg M.S., Williams J.M., Tarbit M., Goldfarb P.S., Gray T.J., Gibson G.G. A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Xenobiotica. 29:1999;269-279.
11. Watkins R.E., Wisely G.B., Moore L.B., Collins J.L., Lambert M.H., Williams S.P., Willson T.M., Kliewer S.A., Redinbo M.R. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science. 292:2001;2329-2333.
12. Lewis D.F.V., Lake B.G. Molecular modelling of the rat peroxisome proliferator-activated receptor-α (rPPARα) by homology with the human retinoic acid X receptor α (hRXRα) and investigation of ligand binding interactions 1: QSARs. Toxicol. In Vitro. 12:1998;619-632.
13. Bourguet et al., 1995.
14. Brzozowski et al., 1998.
15. Bourguet et al., 1995.
16. Brzozowski et al., 1995.
17. Bourguet et al., 1995.