Mechanism of retinoid X receptor partial agonistic action of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5- carboxylic acid and structural development to increase potency

Journal of Medicinal Chemistry

Volumn 56, Issue 5, 2013, Pages 1865-1877

  Ohsawa, Fuminori ^a   Yamada, Shoya ^a,b   Yakushiji, Nobumasa ^a   Shinozaki, Ryosuke ^a   Nakayama, Mariko ^a   Kawata, Kohei ^a   Hagaya, Manabu ^a   Kobayashi, Toshiki ^a   Kohara, Kazutaka ^a   Furusawa, Yuuki ^a   Fujiwara, Chisa ^a   Ohta, Yui ^a   Makishima, Makoto ^c   Naitou, Hirotaka ^d   Tai, Akihiro ^e   Yoshikawa, Yutaka ^f   Yasui, Hiroyuki ^f   Kakuta, Hiroki ^a  

^a OKAYAMA UNIVERSITY   (Japan)

^b JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE   (Japan)

^c NIHON UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^d UNIVERSITY OF SHIZUOKA   (Japan)

^e PREFECTURAL UNIVERSITY OF HIROSHIMA   (Japan)

^f KYOTO PHARMACEUTICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRO 2 NAPHTHYL) 1H BENZOTRIAZOLE 5 CARBOXYLIC ACID; 1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRO 2 NAPHTHYL) 2 THIOXO 2,3 DIHYDRO 1H BENZOIMIDAZOLE 5 CARBOXYLIC ACID; 1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRONAPHTHALEN 2 YL) 1H INDOLE 5 CARBOXYLIC ACID; 1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRONAPHTHALEN 2 YL) TRIFLUOROMETHYL 1H BENZOIMIDAZOLE 5 CARBOXYLIC ACID; 2 AMINO 1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRONAPHTHALEN 2 YL) 1H BENZOIMIDAZOLE 5 CARBOXYLIC ACID; 2 METHYL 1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRO 2 NAPHTHYL) 1H BENZOIMIDAZOLE 5 CARBOXYLIC ACID; 2 OXO 1 (3,5,5,8,8 PENTAMETHYL 5,6,7,8 TETRAHYDRO 2 NAPHTHYL) 2,3 DIHYDRO 1H BENZOIMIDAZOLE 5 CARBOXYLIC ACID; 6 [ETHYL(5,5,8,8 TETRAMETHYL 5,6,7,8 TETRAHYDRONAPHTHALEN 2 YL) AMINO]NICOTINIC ACID; ANTIDIABETIC AGENT; BEXAROTENE; FLUORESCEIN; PARTIAL AGONIST; RETINOID X RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIDIABETIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; FEMALE; FLUORESCENCE; MALE; MOLECULAR DOCKING; MOUSE; NONHUMAN; POLARIZATION; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

ANIMALS; CERCOPITHECUS AETHIOPS; COS CELLS; DIABETES MELLITUS, TYPE 2; HYPOGLYCEMIC AGENTS; MICE; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; RETINOID X RECEPTORS; TETRAHYDRONAPHTHALENES; TRIAZOLES;

EID: 84875181914     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400033f     Document Type: Article

References (37)

1. Svensson, S.; Ostberg, T.; Jacobsson, M.; Norström, C.; Stefansson, K.; Hallén, D.; Johansson, I. C.; Zachrisson, K.; Ogg, D.; Jendeberg, L. Crystal structure of the heterodimeric complex of LXRα and RXRβ ligand-binding domains in a fully agonistic conformation EMBO J. 2003, 22, 4625-4633 (Pubitemid 37162899)
2. de Lera, A. R.; Bourguet, W.; Altucci, L.; Gronemeyer, H. Design of selective nuclear receptor modulators: RAR and RXR as a case study Nat. Rev. Drug Discovery 2007, 6, 811-820 (Pubitemid 47504872)
3. Mangelsdorf, D. J.; Evans, R. M. The RXR heterodimers and orphan receptors Cell 1995, 83, 841-850 (Pubitemid 26006526)
4. Su, C. G.; Wen, X.; Bailey, S. T.; Jiang, W.; Rangwala, S. M.; Keilbaugh, S. A.; Flanigan, A.; Murthy, S.; Lazar, M. A.; Wu, G. D. A novel therapy for colitis utilizing PPARγ ligands to inhibit the epithelial inflammatory response J. Clin. Invest. 1999, 104, 383-389 (Pubitemid 29534322)
5. Chao, E. Y.; Caravella, J. A.; Watson, M. A.; Campobasso, N.; Ghisletti, S.; Billin, A. N.; Galardi, C.; Wang, P.; Laffitte, B. A.; Iannone, M. A.; Goodwin, B. J.; Nichols, J. A.; Parks, D. J.; Stewart, E.; Wiethe, R. W.; Williams, S. P.; Smallwood, A.; Pearce, K. H.; Glass, C. K.; Willson, T. M.; Zuercher, W. J.; Collins, J. L. Structure-guided design of N -phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity J. Med. Chem. 2008, 51, 5758-5765
6. Pascual, G.; Fong, A. L.; Ogawa, S.; Gamliel, A.; Li, A. C.; Perissi, V.; Rose, D. W.; Willson, T. M.; Rosenfeld, M. G.; Glass, C. K. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPARγ Nature 2005, 437, 759-763 (Pubitemid 41486547)
7. Mitro, N.; Mak, P. A.; Vargas, L.; Godio, C.; Hampton, E.; Molteni, V.; Kreusch, A.; Saez, E. The nuclear receptor LXR is a glucose sensor Nature 2007, 445, 219-223 (Pubitemid 46095727)
8. Commerford, S. R.; Vargas, L.; Dorfman, S. E.; Mitro, N.; Rocheford, E. C.; Mak, P. A.; Li, X.; Kennedy, P.; Mullarkey, T. L.; Saez, E. Dissection of the insulin-sensitizing effect of liver X receptor ligands Mol. Endocrinol. 2007, 21, 3002-3012 (Pubitemid 350223510)
9. Joseph, S. B.; Castrillo, A.; Laffitte, B. A.; Mangelsdorf, D. J.; Tontonoz, P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors Nat. Med. 2003, 9, 213-219 (Pubitemid 36227724)
10. Fowler, A. J.; Sheu, M. Y.; Schmuth, M.; Kao, J.; Fluhr, J. W.; Rhein, L.; Collins, J. L.; Willson, T. M.; Mangelsdorf, D. J.; Elias, P. M.; Feingold, K. R. Liver X receptor activators display antiinflammatory activity in irritant and allergic contact dermatitis models: Liver-X-receptor-specific inhibition of inflammation and primary cytokine production J. Invest. Dermatol. 2003, 120, 246-255 (Pubitemid 36513075)
11. Shulman, A. I.; Larson, C.; Mangelsdorf, D. J.; Ranganathan, R. Structural determinants of allosteric ligand activation in RXR heterodimers Cell 2004, 116, 417-429 (Pubitemid 38366318)
12. Gniadecki, R.; Assaf, C.; Bagot, M.; Dummer, R.; Duvic, M.; Knobler, R.; Ranki, A.; Schwandt, P.; Whittaker, S. The optimal use of bexarotene in cutaneous T-cell lymphoma Br. J. Dermatol. 2007, 157, 433-440 (Pubitemid 47256108)
13. Boehm, M. F.; Zhang, L.; Badea, B. A.; White, S. K.; Mais, D. E.; Berger, E.; Suto, C. M.; Goldman, M. E.; Heyman, R. A. Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids J. Med. Chem. 1994, 37, 2930-2941 (Pubitemid 24297810)
14. Fujii, S.; Ohsawa, F.; Yamada, S.; Shinozaki, R.; Fukai, R.; Makishima, M.; Enomoto, S.; Tai, A.; Kakuta, H. Modification at the acidic domain of RXR agonists has little effect on permissive RXR heterodimer activation Bioorg. Med. Chem. Lett. 2010, 20, 5139-5142
15. Takamatsu, K.; Takano, A.; Yakushiji, N.; Morohashi, K.; Morishita, K.; Matsuura, N.; Makishima, M.; Tai, A.; Sasaki, K.; Kakuta, H. The first potent subtype-selective retinoid X receptor (RXR) agonist possessing a 3-isopropoxy-4-isopropylphenylamino moiety, NEt-3IP (RXRα/β-dual agonist) ChemMedChem 2008, 3, 780-787
16. Kakuta, H.; Yakushiji, N.; Shinozaki, R.; Ohsawa, F.; Yamada, S.; Ohta, Y.; Kawata, K.; Nakayama, M.; Hagaya, M.; Fujiwara, C.; Makishima, K.; Uno, S.; Tai, A.; Maehara, A.; Nakayama, M.; Oohashi, T.; Yasui, H.; Yoshikawa, Y. RXR partial agonist CBt-PMN exerts therapeutic effects on type 2 diabetes without the side effects of RXR full agonists ACS Med. Chem. Lett. 2012, 3, 427-432
17. Pogenberg, V.; Guichou, J. F.; Vivat-Hannah, V.; Kammerer, S.; Pérez, E.; Germain, P.; de Lera, A. R.; Gronemeyer, H.; Royer, C. A.; Bourguet, W. Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropystudies J. Biol. Chem. 2005, 280, 1625-1633
18. Li, X.; Hansen, P. A.; Xi, L.; Chandraratna, R. A.; Burant, C. F. Distinct mechanisms of glucose lowering by specific agonists for peroxisomal proliferator activated receptor gamma and retinoic acid X receptors J. Biol. Chem. 2005, 280, 38317-38327 (Pubitemid 43860306)
19. Lenhard, J. M.; Lancaster, M. E.; Paulik, M. A.; Weiel, J. E.; Binz, J. G.; Sundseth, S. S.; Gaskill, B. A.; Lightfoot, R. M.; Brown, H. R. The RXR agonist LG100268 causes hepatomegaly, improves glycaemic control and decreases cardiovascular risk and cachexia in diabetic mice suffering from pancreatic beta-cell dysfunction Diabetologia 1999, 42, 545-554 (Pubitemid 29196004)
20. Davies, P. J.; Berry, S. A.; Shipley, G. L.; Eckel, R. H.; Hennuyer, N.; Crombie, D. L.; Ogilvie, K. M.; Peinado-Onsurbe, J.; Fievet, C.; Leibowitz, M. D.; Heyman, R. A.; Auwerx, J. Metabolic effects of rexinoids: Tissue-specific regulation of lipoprotein lipase activity Mol. Pharmacol. 2001, 59, 170-176 (Pubitemid 32108547)
21. Ohsawa, F.; Morishita, K.; Yamada, S.; Makishima, M.; Kakuta, H. Modification at the lipophilic domain of RXR agonists differentially influences activation of RXR heterodimers ACS Med. Chem. Lett. 2010, 1, 521-525
22. y type 2 diabetes model mice Biol. Pharm. Bull. 2012, 35, 629-633
23. Qing, F. L.; Yue, X. J. A novel synthesis of 9,13-di -cis double bonds locked retinoids Tetrahedron Lett. 1997, 38, 8067-8070
24. Germain, P.; Staels, B.; Dacquet, C.; Spedding, M.; Laudet, V. Overview of nomenclature of nuclear receptors Pharmacol. Rev. 2006, 58, 685-704 (Pubitemid 44833739)
25. Oberfield, J. L.; Collins, J. L.; Holmes, C. P.; Goreham, D. M.; Cooper, J. P.; Cobb, J. E.; Lenhard, J. M.; Hull-Ryde, E. A.; Mohr, C. P.; Blanchard, S. G.; Parks, D. J.; Moore, L. B.; Lehmann, J. M.; Plunket, K.; Miller, A. B.; Milburn, M. V.; Kliewer, S. A.; Willson, T. M. A peroxisome proliferator- activated receptor gamma ligand inhibits adipocyte differentiation Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 6102-6106 (Pubitemid 29256626)
26. Egea, P. F.; Mitschler, A.; Rochel, N.; Ruff, M.; Chambon, P.; Moras, D. Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9- cis Retinoic acid EMBO J. 2000, 19, 2592-2601 (Pubitemid 30323548)
27. Lévy-Bimbot, M.; Major, G.; Courilleau, D.; Blondeau, J.; Lévi, Y. Tetrabromobisphenol-A disrupts thyroid hormone receptor alpha function in vitro: Use of fluorescence polarization to assay corepressor and coactivator peptide binding Chemosphere 2012, 87, 782-788
28. Ozers, M. S.; Ervin, K. M.; Steffen, C. L.; Fronczak, J. A.; Lebakken, C. S.; Carnahan, K. A.; Lowery, R. G.; Burke, T. J. Analysis of ligand-dependent recruitment of coactivator peptides to estrogen receptor using fluorescence polarization Mol. Endcrinol. 2005, 19, 25-34 (Pubitemid 40065956)
29. Stafslien, D. K.; Vedvik, K. L.; Rosier, T.; Ozers, M. S. Analysis of ligand-dependent recruitment of coactivator peptides to RXRβ in a time-resolved fluorescence resonance energy transfer assay Mol. Cell. Endocrinol. 2007, 264, 82-89 (Pubitemid 46097305)
30. Ghosh, J. C.; Yang, X.; Zhang, A.; Lambert, M. H.; Li, H.; Xu, H. E.; Chen, J. D. Interactions that determine the assembly of a retinoid X receptor/corepressor complex Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 5842-5847 (Pubitemid 34493227)
31. Takahashi, B.; Ohta, K.; Kawachi, E.; Fukasawa, H.; Hashimoto, Y.; Kagechika, H. Novel retinoid X receptor antagonists: Specific inhibition of retinoid synergism in RXR-RAR heterodimer actions J. Med. Chem. 2002, 45, 3327-3330 (Pubitemid 34824021)
32. Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility J. Comput. Chem. 2009, 30, 2785-2791
33. Kain, S. R. Use of secreted alkaline phosphatase as a reporter of gene expression in mammalian cells Methods Mol. Biol. 1997, 63, 49-60
34. Landy, A. Dynamic, structural, and regulatory aspects of lambda site-specific recombination Annu. Rev. Biochem. 1989, 58, 913-949 (Pubitemid 19172991)
35. Walhout, A. J.; Temple, G. F.; Brasch, M. A.; Hartley, J. L.; Lorson, M. A.; van den Heuvel, S.; Vidal, M. GATEWAY recombinational cloning: Application to the cloning of large numbers of open reading frames or ORFeomes Methods Enzymol. 2000, 328, 575-592
36. Liang, F.; Matrubutham, U.; Parvizi, B.; Yen, J.; Duan, D.; Mirchandani, J.; Hashima, S.; Nguyen, U.; Ubil, E.; Loewenheim, J.; Yu, X.; Sipes, S.; Williams, W.; Wang, L.; Bennett, R.; Carrino, J. ORFDB: An information resource linking scientific content to a high-quality open reading frame (ORF) collection Nucleic Acids Res. 2004, 32, D595-D599
37. Hengen, P. Purification of His-Tag fusion proteins from Escherichia coli Trends Biochem. Sci. 1995, 20, 285-286