Identification of a high-affinity ligand that exhibits complete aryl hydrocarbon receptor antagonism

Journal of Pharmacology and Experimental Therapeutics

Volumn 338, Issue 1, 2011, Pages 318-327

  Smith, Kayla J ^a   Murray, Iain A ^a   Tanos, Rachel ^a   Tellew, John ^b   Boitano, Anthony E ^b   Bisson, William H ^c   Kolluri, Siva K ^d   Cooke, Michael P ^b   Perdew, Gary H ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^c UNIVERSITY OF GENEVA   (Switzerland)

^d OREGON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; CELL PROTEIN; GNF 351; MESSENGER RNA; N [2 (1H INDOL 3 YL)ETHYL] 9 ISOPROPYL 2 (5 METHYLPYRIDIN 3 YL) 9H PURIN 6 AMINE; PROTEIN SAA1; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; BINDING COMPETITION; CELL STRAIN HEPG2; CELL STRAIN HUH7; COMPUTER MODEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIOXIN RESPONSIVE ELEMENT; DNA RESPONSIVE ELEMENT; DRUG STRUCTURE; EAR DISEASE; EAR EDEMA; GENE EXPRESSION REGULATION; HEPATOMA CELL; HUMAN; HUMAN CELL; LIGAND BINDING; MALE; MOUSE; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN FUNCTION; RECEPTOR BLOCKING; REPORTER GENE; SIGNAL TRANSDUCTION;

ALLYL COMPOUNDS; ANIMALS; BINDING SITES; CELL LINE, TUMOR; DOSE-RESPONSE RELATIONSHIP, DRUG; HEP G2 CELLS; HEPATOCYTES; HUMANS; INDAZOLES; INDOLES; LIGANDS; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PURINES; RECEPTORS, ARYL HYDROCARBON;

EID: 79959509068     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.178392     Document Type: Article

References (25)

1. References Beischlag TV, Luis Morales J, Hollingshead BD, and Perdew GH (2008) The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 18:207-250. (Pubitemid 351620286)
2. Bisson WH, Koch DC, O'Donnell EF, Khalil SM, Kerkvliet NI, Tanguay RL, Abagyan R, and Kolluri SK (2009) Modeling of the aryl hydrocarbon receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands. J Med Chem 52:5635-5641.
3. Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE, Walker JR, Flaveny CA, Perdew GH, Denison MS, et al. (2010) Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 329:1345-1348.
4. Casper RF, Quesne M, Rogers IM, Shirota T, Jolivet A, Milgrom E, and Savouret JF (1999) Resveratrol has antagonist activity on the aryl hydrocarbon receptor: implications for prevention of dioxin toxicity. Mol Pharmacol 56:784-790. (Pubitemid 29491181)
5. DiNatale BC, Schroeder JC, Francey LJ, Kusnadi A, and Perdew GH (2010) Mechanistic insights into the events that lead to synergistic induction of interleukin 6 transcription upon activation of the aryl hydrocarbon receptor and inflammatory signaling. J Biol Chem 285:24388-24397.
6. Flaveny CA, Murray IA, Chiaro CR, and Perdew GH (2009) Ligand selectivity and gene regulation by the human aryl hydrocarbon receptor in transgenic mice. Mol Pharmacol 75:1412-1420.
7. Garrison PM, Tullis K, Aarts JM, Brouwer A, Giesy JP, and Denison MS (1996) Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. Fundam Appl Toxicol 30:194-203.
8. Kim SH, Henry EC, Kim DK, Kim YH, Shin KJ, Han MS, Lee TG, Kang JK, Gasiewicz TA, Ryu SH, et al. (2006) Novel compound 2-methyl-2H-pyrazole-3- carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor. Mol Pharmacol 69:1871-1878. (Pubitemid 43894303)
9. Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, and Kishimoto T (2008) Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. Proc Natl Acad Sci USA 105:9721-9726. (Pubitemid 352031367)
10. Long WP, Pray-Grant M, Tsai JC, and Perdew GH (1998) Protein kinase C activity is required for aryl hydrocarbon receptor pathway-mediated signal transduction. Mol Pharmacol 53:691-700. (Pubitemid 28196492)
11. Lu YF, Santostefano M, Cunningham BD, Threadgill MD, and Safe S (1995) Identification of 3′-methoxy-4′-nitroflavone as a pure aryl hydrocarbon (Ah) receptor antagonist and evidence for more than one form of the nuclear Ah receptor in MCF-7 human breast cancer cells. Arch Biochem Biophys 316:470-477.
12. Murray IA, Flaveny CA, Chiaro CR, Sharma AK, Tanos RS, Schroeder JC, Amin SG, Bisson WH, Kolluri SK, and Perdew GH (2011) Suppression of cytokine-mediated complement factor gene expression through selective activation of the Ah receptor with 3′,4′-dimethoxy-α-naphthoflavone. Mol Pharmacol 79:508-519.
13. Murray IA, Flaveny CA, DiNatale BC, Chairo CR, Schroeder JC, Kusnadi A, and Perdew GH (2010a) Antagonism of aryl hydrocarbon receptor signaling by 6,2′,4′-trimethoxyflavone. J Pharmacol Exp Ther 332:135-144.
14. Murray IA, Krishnegowda G, DiNatale BC, Flaveny C, Chiaro C, Lin JM, Sharma AK, Amin S, and Perdew GH (2010b) Development of a selective modulator of aryl hydrocarbon (Ah) receptor activity that exhibits anti-inflammatory properties. Chem Res Toxicol 23:955-966.
15. Murray IA, Morales JL, Flaveny CA, Dinatale BC, Chiaro C, Gowdahalli K, Amin S, and Perdew GH (2010c) Evidence for ligand-mediated selective modulation of aryl hydrocarbon receptor activity. Mol Pharmacol 77:247-254.
16. Patel RD, Murray IA, Flaveny CA, Kusnadi A, and Perdew GH (2009) Ah receptor represses acute-phase response gene expression without binding to its cognate response element. Lab Invest 89:695-707.
17. Poland A, Glover E, Ebetino H, and Kende A (1986) Photoaffinity labelling of the Ah receptor. Food Chem Toxicol 24:781-787. (Pubitemid 17184072)
18. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, and Weiner HL (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453:65-71. (Pubitemid 351630328)
19. Safe S and McDougal A (2002) Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (Review). Int J Oncol 20:1123-1128.
20. Schmidt JV and Bradfield CA (1996) Ah receptor signaling pathways. Annu Rev Cell Dev Biol 12:55-89. (Pubitemid 26422709)
21. Schroeder JC, Dinatale BC, Murray IA, Flaveny CA, Liu Q, Laurenzana EM, Lin JM, Strom SC, Omiecinski CJ, Amin S, et al. (2010) The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 49:393-400.
22. Veldhoen M, Hirota K, Christensen J, O'Garra A, and Stockinger B (2009) Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med 206:43-49.
23. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, and Stockinger B (2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453:106-109. (Pubitemid 351630329)
24. Wilhelmsson A, Whitelaw ML, Gustafsson JA, and Poellinger L (1994) Agonistic and antagonistic effects of α-naphthoflavone on dioxin receptor function. Role of the basic region helix-loop-helix dioxin receptor partner factor Arnt. J Biol Chem 269:19028-19033.
25. Zhao B, Degroot DE, Hayashi A, He G, and Denison MS (2010) CH223191 is a ligand-selective antagonist of the Ah (Dioxin) receptor. Toxicol Sci 117:393-403.