Evaluation of in vitro PXR-based assays and in silico modeling approaches for understanding the binding of a structurally diverse set of drugs to PXR

Biochemical Pharmacology

Volumn 81, Issue 5, 2011, Pages 669-679

  Xiao, Li ^a   Nickbarg, Elliott ^a   Wang, Wenyan ^a   Thomas, Ann ^a   Ziebell, Michael ^a   Prosise, Winfred W ^a   Lesburg, Charles A ^a   Taremi, S Shane ^a   Gerlach, Valerie L ^a   Le, Hung V ^a   Cheng, K C ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

CYP3A induction; In vitro assays; Pregnane X receptor

Indexed keywords

AMLODIPINE; CARBAMAZEPINE; CLOTRIMAZOLE; CYTOCHROME P450 3A; DEXAMETHASONE; DICLOFENAC; DOXORUBICIN; FELODIPINE; HALOPERIDOL; HYPERFORIN; ISRADIPINE; LACIDIPINE; LANSOPRAZOLE; MIFEPRISTONE; NAPROXEN; NICARDIPINE; NIFEDIPINE; NIMODIPINE; NISOLDIPINE; OMEPRAZOLE; PHENYLBUTAZONE; PHENYTOIN; PIOGLITAZONE; PREGNANE X RECEPTOR; PREGNENOLONE; RIFABUTIN; RIFAMPICIN; RITONAVIR; ROSIGLITAZONE; UNINDEXED DRUG;

ARTICLE; BINDING SITE; CIRCULAR DICHROISM; COMPLEX FORMATION; COMPUTER MODEL; CORRELATION COEFFICIENT; CRYSTAL STRUCTURE; DRUG RECEPTOR BINDING; ENZYME INDUCTION; HYDROGEN BOND; HYDROPHOBICITY; IN VITRO STUDY; LIGAND BINDING; MOLECULAR WEIGHT; PRIORITY JOURNAL; REPORTER GENE; TEMPERATURE DEPENDENCE; THREE DIMENSIONAL IMAGING;

CIRCULAR DICHROISM; GENES, REPORTER; HEP G2 CELLS; HUMANS; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; LIGANDS; LUCIFERASES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MOLECULAR WEIGHT; NUCLEAR RECEPTOR COACTIVATORS; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING; RECEPTORS, STEROID; STRUCTURE-ACTIVITY RELATIONSHIP; TEMPERATURE;

EID: 79551490503     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2010.12.003     Document Type: Article

References (28)

1. W.E. Evans, and M.V. Relling Pharmacogenomics: translating functional genomics to rational therapeutics Science 286 1999 487 491
2. X. Cui, A. Thomas, V. Gerlach, R.E. White, R.A. Morrison, and K.-C. Cheng Application and interpretation of hPXR screening data: validation of reporter signal requirements for prediction of clinically relevant CYP3A4 inducers Biochem Pharmacol 76 2008 680 689
3. S.A. Kliewer, J.T. Moore, L. Wade, J.L. Staudinger, M.A. Watson, and S.A. Jones An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway Cell 92 1998 73 82
4. T.M. Wilson, and S.A. Kliewer PXR, CAR and drug metabolism Nat Rev Drug Discov 4 2002 259 266
5. J.T. Moore, and S.A. Kliewer Use of the nuclear receptor PXR to predict drug interactions Toxicology 153 2000 1 10
6. R.E. Watkins, P.R. Davis-Searles, M.H. Lambert, and M.R. Redinbo J Mol Biol 331 2003 815 828
7. B.D. Darimont, R.L. Wagner, J.W. Apriletti, M.R. Stallcup, P.J. Kushner, and J.D. Baxter Structure and specificity of nuclear receptor-coactivator interactions Development 12 1998 3343 3356
8. H.E. Xu, M.H. Lambert, V.G. Montana, K.D. Plunket, L.B. Moore, and J.L. Collins Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors Proc Natl Acad Sci U S A 98 2001 13919 13924
9. W. Wang, W.W. Prosise, L. Chen, S.S. Taremi, H.V. Le, and V. Madison Construction of a fully active PXR-SRC1 tethered protein with increased stability Protein Eng Des Sel 21 2008 425 433
10. J. Raucy, L. Warfe, M.F. Yueh, and S.W. Allen A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system J Pharmacol Exp Ther 303 2002 412 423
11. X. Cui, A. Thomas, Y. Han, J. Palamanda, D. Montgomery, and R.E. White Quantitative PCR assay for cytochrome P-450 2B and 3A induction in rat precision-cut liver slices: correlation study with induction in vivo J Pharmacol Toxicol Methods 52 2005 234 243
12. J. Chen, C. Tran, L. Xiao, J. Palamanda, T. Klapmuts, and P. Kumari Co-induction of CYP3A12 and 3A26 in dog liver slice by xenobiotics: species difference between human and dog CYP 3A induction Drug Metab Lett 3 2009 290 297
13. R.E. Watkins, G.B. Wisely, L.B. Moore, J.L. Collins, M.H. Lambert, and S.P. Williams The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity Science 292 2001 2329 2333
14. R.E. Watkins, J.M. Maglich, L.B. Moore, G.B. Wisely, S.M. Noble, and P.R. Davis-Searles 2.1 crystal structure of human PXR in complex with the St. John's wort compound hyperforin Biochemistry 42 2003 1430 1438
15. R.E. Watkins, S.M. Noble, and M.R. Redinbo Structural insights into the promiscuity and function of the human pregnane X receptor Curr Opin Drug Discov Dev 5 2002 150 158
16. S. Ekins, V. Kholodovych, N. Ai, M. Sinz, J. Gal, and L. Gera Computational discovery of novel low micromolar human pregnane X receptor antagonists Mol Pharmacol 74 2008 662 672
17. M.N. Jacobs In silico tools to aid risk assessment of endocrine disrupting chemicals Toxicology 205 2004 43 53
18. C.Y. Ung, H. Li, C.W. Yap, and Y.Z. Chen In silico prediction of pregnane X receptor activators by machine learning approaches Mol Pharmacol 71 2007 158 168
19. D.A. Annis, J. Athanasopoulos, P.J. Curran, J.S. Felsch, K. Kalghatgi, and W.H. Lee An affinity selection-mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries. Discovery of a novel antagonist of E. coli dihydrofolate reductase Int J Mass Spectrom 238 2004 77 83
20. A. Annis, C.C. Chuang, and N. Nazef ALIS: an affinity selection-mass spectrometry system for the discovery and characterization of protein-ligand interactions Methods and Principles in Medicinal Chemistry: Mass Spectrometry in Medicinal Chemistry 36 2007 121 156
21. D.A. Annis, N. Nazef, C.C. Chuang, M.P. Scott, and H.M. Nash A general technique to rank protein-ligand binding affinities and determine allosteric vs. direct binding site competition in compound mixtures J Am Chem Soc 126 2004 15495 15503
22. D.A. Annis, G.W. Shipps, Y. Deng, J. Popvici-Muller, M.A. Siddiqui, and P.J. Curran Method for quantitative protein-ligand affinity measurements in compound mixtures Anal Chem 79 2007 4538 4542
23. O. Buczek, D. Krowarsch, and J. Otlewski Thermodynamics of single peptide bond cleavage in bovine pancreatic trypsin inhibitor (BPTI) Protein Sci 11 2002 924 932
24. S.A. Kliewer, B. Goodwin, and T.M. Wilson The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism Endocr Rev 5 2002 687 702
25. R.M. Evans The nuclear receptor superfamily: a rosetta stone for physiology Mol Endocrinol 196 2005 1429 1438
26. R.T. Nolte, G.B. Wisely, S. Westin, J.E. Cobb, M.H. Lambert, and R. Kurokawa Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma Nature 395 1998 137 143
27. R.T. Gampe, V.G. Montana, M.H. Lambert, A.B. Miller, R.K. Bledsoe, and M.V. Milburn Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors Mol Cell 5 2000 545 555
28. L. Xiao, X. Cui, V. Madison, R.E. White, and K.-C. Cheng Insights from a three-dimensional model into ligand binding to constitutive active receptor Drug Metab Disp 30 2002 951 956