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PPAR Research
Volume 2015, Article ID 254560, 6 pages
http://dx.doi.org/10.1155/2015/254560
Research Article

Identification of Bexarotene as a PPAR Antagonist with HDX

Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA

Received 26 June 2015; Accepted 23 August 2015

Academic Editor: John B. Bruning

Copyright © 2015 David P. Marciano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. J. Mangelsdorf and R. M. Evans, “The RXR heterodimers and orphan receptors,” Cell, vol. 83, no. 6, pp. 841–850, 1995. View at Publisher · View at Google Scholar · View at Scopus
  2. P. Lefebvre, Y. Benomar, and B. Staels, “Retinoid X receptors: common heterodimerization partners with distinct functions,” Trends in Endocrinology and Metabolism, vol. 21, no. 11, pp. 676–683, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. I. G. Schulman, C. Li, J. W. R. Schwabe, and R. M. Evans, “The phantom ligand effect: allosteric control of transcription by the retinoid X receptor,” Genes & Development, vol. 11, no. 3, pp. 299–308, 1997. View at Publisher · View at Google Scholar · View at Scopus
  4. R. M. Cesario, K. Klausing, H. Razzaghi et al., “The rexinoid LG100754 is a novel RXR:PPARγ agonist and decreases glucose levels in vivo,” Molecular Endocrinology, vol. 15, no. 8, pp. 1360–1369, 2001. View at Publisher · View at Google Scholar · View at Scopus
  5. E. Pérez, W. Bourguet, H. Gronemeyer, and A. R. de Lera, “Modulation of RXR function through ligand design,” Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, vol. 1821, no. 1, pp. 57–69, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. M.-J. Sanz, F. Albertos, E. Otero, M. Juez, E. J. Morcillo, and L. Piqueras, “Retinoid X receptor agonists impair arterial mononuclear cell recruitment through peroxisome proliferator-activated receptor-γ activation,” Journal of Immunology, vol. 189, no. 1, pp. 411–424, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. J. M. Lehmann, L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer, “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ),” The Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Mukherjee, P. J. A. Davies, D. L. Crombie et al., “Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists,” Nature, vol. 386, no. 6623, pp. 407–410, 1997. View at Publisher · View at Google Scholar · View at Scopus
  9. H. S. Ahuja, S. Liu, D. L. Crombie et al., “Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents,” Molecular Pharmacology, vol. 59, no. 4, pp. 765–773, 2001. View at Google Scholar · View at Scopus
  10. J. M. Lenhard, M. E. Lancaster, M. A. Paulik et al., “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, vol. 42, no. 5, pp. 545–554, 1999. View at Publisher · View at Google Scholar · View at Scopus
  11. K. M. Ogilvie, R. Saladin, T. R. Nagy, M. S. Urcan, R. A. Heyman, and M. D. Leibowitz, “Activation of the retinoid X receptor suppresses appetite in the rat,” Endocrinology, vol. 145, no. 2, pp. 565–573, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. M. D. Leibowitz, R. J. Ardecky, M. F. Boehm et al., “Biological characterization of a heterodimer-selective retinoid X receptor modulator: potential benefits for the treatment of type 2 diabetes,” Endocrinology, vol. 147, no. 2, pp. 1044–1053, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. K. K. Ryan, B. Li, B. E. Grayson, E. K. Matter, S. C. Woods, and R. J. Seeley, “A role for central nervous system PPAR-γ in the regulation of energy balance,” Nature Medicine, vol. 17, no. 5, pp. 623–626, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. M. F. Boehm, L. Zhang, L. Zhi et al., “Design and synthesis of potent retinoid X receptor selective ligands that induce apoptosis in leukemia cells,” Journal of Medicinal Chemistry, vol. 38, no. 16, pp. 3146–3155, 1995. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Gniadecki, C. Assaf, M. Bagot et al., “The optimal use of bexarotene in cutaneous T-cell lymphoma,” British Journal of Dermatology, vol. 157, no. 3, pp. 433–440, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. S. C. Yanik, A. H. Baker, K. K. Mann, and J. J. Schlezinger, “Organotins are potent activators of PPARγ and adipocyte differentiation in bone marrow multipotent mesenchymal stromal cells,” Toxicological Sciences, vol. 122, no. 2, pp. 476–488, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. M. J. Chalmers, S. A. Busby, B. D. Pascal et al., “Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry,” Analytical Chemistry, vol. 78, no. 4, pp. 1005–1014, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. J. H. Choi, A. S. Banks, T. M. Kamenecka et al., “Antidiabetic actions of a non-agonist PPARgamma ligand blocking Cdk5-mediated phosphorylation,” Nature, vol. 477, no. 7365, pp. 477–481, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. B. D. Pascal, S. Willis, J. L. Lauer et al., “HDX workbench: software for the analysis of H/D exchange MS data,” Journal of the American Society for Mass Spectrometry, vol. 23, no. 9, pp. 1512–1521, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Liu, K. M. Ogilvie, K. A. Y. Klausing et al., “Mechanism of selective retinoid X receptor agonist-induced hypothyroidism in the rat,” Endocrinology, vol. 143, no. 8, pp. 2880–2885, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. D. P. Marciano, D. S. Kuruvilla, S. V. Boregowda et al., “Pharmacological repression of PPARγ promotes osteogenesis,” Nature Communications, vol. 6, article 7443, 2015. View at Publisher · View at Google Scholar
  22. M. Wadman, “New cures sought from old drugs,” Nature, vol. 490, no. 7418, p. 15, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. J. S. Shim and J. O. Liu, “Recent advances in drug repositioning for the discovery of new anticancer drugs,” International Journal of Biological Sciences, vol. 10, no. 7, pp. 654–663, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Chiellini, J. W. Apriletti, H. A. Yoshihara, J. D. Baxter, R. C. J. Ribeiro, and T. S. Scanlan, “A high-affinity subtype-selective agonist ligand for the thyroid hormone receptor,” Chemistry and Biology, vol. 5, no. 6, pp. 299–306, 1998. View at Publisher · View at Google Scholar · View at Scopus
  25. A. K. Shiau, D. Barstad, J. T. Radek et al., “Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism,” Nature Structural Biology, vol. 9, no. 5, pp. 359–364, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. S. A. F. Morad, J. C. Levin, S.-F. Tan, T. E. Fox, D. J. Feith, and M. C. Cabot, “Novel off-target effect of tamoxifen—inhibition of acid ceramidase activity in cancer cells,” Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, vol. 1831, no. 12, pp. 1657–1664, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. B. R. Hoffmann, M. F. El-Mansy, D. S. Sem, and A. S. Greene, “Chemical proteomics-based analysis of off-target binding profiles for rosiglitazone and pioglitazone: clues for assessing potential for cardiotoxicity,” Journal of Medicinal Chemistry, vol. 55, no. 19, pp. 8260–8271, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. D. P. Marciano, M. R. Chang, C. A. Corzo et al., “The therapeutic potential of nuclear receptor modulators for treatment of metabolic disorders: PPARγ, RORs, and Rev-erbs,” Cell Metabolism, vol. 19, no. 2, pp. 193–208, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. E. Jacoby, G. Tresadern, S. Bembenek et al., “Extending kinome coverage by analysis of kinase inhibitor broad profiling data,” Drug Discovery Today, vol. 20, no. 6, pp. 652–658, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. J. P. V. Heuvel, “Nutrigenomics and nutrigenetics of ω3 polyunsaturated fatty acids,” Progress in Molecular Biology and Translational Science, vol. 108, pp. 75–112, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. T. P. Burris, L. A. Solt, Y. Wang et al., “Nuclear receptors and their selective pharmacologic modulators,” Pharmacological Reviews, vol. 65, no. 2, pp. 710–778, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. D. P. Marciano, V. Dharmarajan, and P. R. Griffin, “HDX-MS guided drug discovery: small molecules and biopharmaceuticals,” Current Opinion in Structural Biology, vol. 28, pp. 105–111, 2014. View at Publisher · View at Google Scholar · View at Scopus
  33. M. M. Gottardis, E. D. Bischoff, M. A. Shirley, M. A. Wagoner, W. W. Lamph, and R. A. Heyman, “Chemoprevention of mammary carcinoma by LGD1069 (Targretin): an RXR-selective ligand,” Cancer Research, vol. 56, no. 24, pp. 5566–5570, 1996. View at Google Scholar · View at Scopus
  34. P. E. Cramer, J. R. Cirrito, D. W. Wesson et al., “ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models,” Science, vol. 335, no. 6075, pp. 1503–1506, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. J. B. Jahrling, C. M. Hernandez, L. Denner, and K. T. Dineley, “PPARγ recruitment to active ERK during memory consolidation is required for Alzheimer's disease-related cognitive enhancement,” The Journal of Neuroscience, vol. 34, no. 11, pp. 4054–4063, 2014. View at Publisher · View at Google Scholar · View at Scopus