Crystal Structures of the Vitamin D Nuclear Receptor Liganded with the Vitamin D Side Chain Analogues Calcipotriol and Seocalcitol, Receptor Agonists of Clinical Importance. Insights into a Structural Basis for the Switching of Calcipotriol to a Receptor Antagonist by Further Side Chain Modification

Journal of Medicinal Chemistry

Volumn 47, Issue 8, 2004, Pages 1956-1961

  Tocchini Valentini, Giuseppe ^a,b   Rochel, Natacha ^a   Wurtz, Jean Marie ^a   Moras, Dino ^a  

^a INSTITUT DE GÉNÉTIQUE ET DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

^b CNR   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1,3,24 TRIHYDROXY 26,27 CYCLO 9,10 SECOCHOLESTA 5,7,10(19),22 TETRAENE 25 CARBOXYLIC ACID BUTYL ESTER; CALCIPOTRIOL; LEXACALCITOL; SEOCALCITOL; UNCLASSIFIED DRUG; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR; ZK 168281;

ARTICLE; AUTOIMMUNE DISEASE; CANCER; CHEMICAL MODIFICATION; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG ANTAGONISM; DRUG BINDING SITE; DRUG STRUCTURE; INFLAMMATION; LIGAND BINDING; OSTEOPOROSIS; X RAY CRYSTALLOGRAPHY;

CALCITRIOL; CRYSTALLOGRAPHY, X-RAY; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NUCLEAR PROTEINS; RECEPTORS, CALCITRIOL; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 1842607351     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0310582     Document Type: Article

References (27)

1. Bouillon, R.; Okamura, W. H.; Norman A. W. Structure-function relationships in the vitamin D endocrine system. Endocr. Rev. 1995, 16, 200-257.
2. Beckman, M. J.; Deluca, H. F. Modern view of vitamin D3 and its medicinal uses. Prog. Med. Chem. 1998, 35, 1-56.
3. Stein, M. S.; Wark, J. D. An update on the therapeutic potential of vitamin D analogues. Expert Opin. Invest. Drugs 2003, 12 (5), 825-840.
4. Calverley, M. J. Synthesis of MC903, a biologically active vitamin D metabolite analogue. Tetrahedron 1987, 43, 4609-4619.
5. Kragballe, K.; Iversen, L. Calcipotriol. A new topical antipsoriatic. Dermatol. Clin. 1993, 11, 137-141.
6. Mizwicki, M. T.; Norman, A. W. Two key proteins of the vitamin D endocrine system come into crystal clear focus: comparison of the X-ray structures of the nuclear receptor for 1alpha,25-(OH)2 vitamin D3, the plasma vitamin D binding protein, and their ligands. J. Bone Miner. Res. 2003, 18 (5), 795-806.
7. Kissmeyer, A. M.; Binderup, L. Calcipotriol (MC 903): pharmacokinetics in rats and biological activities of metabolites. A comparative study with 1,25(OH)2D3. Biochem. Pharmacol. 1991, 41 (11), 1601-1606.
8. Hansen, C. M.; Hamberg, K. J.; Binderup, E.; Binderup, L. Seocalcitol (EB 1089): A vitamin D analogue of anti-cancer potential. Background, design, synthesis, pre-clinical and clinical evaluation. Curr. Pharm. Des. 2000, 6 (7), 803-828.
9. Colston, K. W.; Mackay, A. G.; James, S. Y.; Binderup, L.; Chander, S.; Coombes, R. C. EB1089: a new vitamin D analogue that inhibits the growth of breast cancer cells in vivo and in vitro. Biochem. Pharmacol. 1992, 44 (12), 2273-2280.
10. Evans, T. R.; Colston, K. W.; Lofts, F. J.; Cunningham, D.; Anthoney, D. A.; Gogas, H.; de Bono, J. S.; Hamberg, K. J.; Skov, T.; Mansi, J. L. A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer. Br. J. Cancer 2002, 86 (5), 680-685.
11. Mangelsdorf, D. J.; Thummel, C.; Beato, M.; Herrlich, P.; Schutz, G.; Umesono, K.; Blumberg, B.; Kastner, P.; Mark, M.; Chambon, P.; et al. The nuclear receptor superfamily: the second decade. Cell 1995, 83, 835-839.
12. Kalkhoven, E.; Valentine, J. E.; Heery, D. M.; Parker, M. G. Isoforms of steroid receptor co-activator 1 differ in their ability to potentiate transcription by the oestrogen receptor. EMBO J. 1998, 17, 232-243.
13. Kamei, Y.; Xu, L.; Heinzel, T.; Torchia, J.; Kurokawa, R.; Gloss, B.; Lin, S. C.; Heyman, R. A.; Rose, D. W.; Glass, C. K.; Rosenfeld, M. G. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1996, 85, 403-414.
14. Rachez, C.; Lemon, B. D.; Suldan, Z.; Bromleigh, V.; Gamble, M.; Naar, A. M.; Erdjument-Bromage, H.; Tempst, P.; Freedman, L. P. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 1999, 398, 824-828.
15. Rochel, N.; Wurtz, J. M.; Mitschler, A.; Klaholz, B.; Moras, D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 2000, 5, 173-179.
16. Tocchini-Valentini, G.; Rochel, N.; Wurtz, J. M.; Mitschler, A.; Moras, D. Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 5491-5496.
17. Wiesinger, H.; Ulrich, M.; Fähnrich, M.; Haberey, M.; Neef, G.; Schwarz, K.; Kirsch, G.; Langer, G.; Thieroff-Ekerdt, R.; Steinmeyer, A. A novel vitamin D receptor partial agonist. J. Invest. Dermatol. 1998, 110, 532.
18. Vaisanen, S.; Ryhanen, S.; Saarela, J. T.; Perakyla, M.; Andersin, T.; Maenpaa, P. H. Structurally and functionally important amino acids of the agonistic conformation of the human vitamin D receptor. Mol. Pharmacol. 2002, 62, 788-794.
19. Rochel, N.; Tocchini-Valentini, G.; Egea, P. F.; Juntunen, K.; Garnier, J. M.; Vihko, P.; Moras, D. Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor. Eur. J. Biochem. 2001, 268, 971-979.
20. Ishizuka, S.; Miura, D.; Ozono, K.; Chokki, M.; Mimura, H.; Norman, A. W. Antagonistic Actions in Vivo of (23S)-25-Dehydro-1alpha-Hydroxyvitamin D(3-)26,23-Lactone on Calcium Metabolism Induced by 1alpha,25-Dihydroxyvitamin D(3). Endocrinology 2001, 142 (1), 59-67.
21. Herdick, M.; Steinmeyer, A.; Carlberg, C. Carboxylic ester antagonists of 1alpha,25-dihydroxyvitamin D(3) show cell-specific actions. Chem. Biol. 2000, 7 (11), 885-894.
22. Pike, A. C.; Brzozowski, A. M.; Walton, J.; Hubbard, R. E.; Thorsell, A. G.; Li, Y. L.; Gustafsson, J. A.; Carlquist, M. Structural insights into the mode of action of a pure antiestrogen. Structure 2001, 9 (2), 145-153.
23. Bury, Y.; Steinmeyer, A.; Carlberg, C. Structure activity relationship of carboxylic ester antagonists of the vitamin D(3) receptor. Mol. Pharmacol. 2000, 58, 1067-1074.
24. Otwinowski, Z.; Minor, W. Processing X-ray data collected in oscillation mode. Methods Enzymol. 1997, 276, 307-326.
25. Brunger, A. T.; Adams, P. D.; Clore, G. M.; DeLano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1998, 54, 905-921.
26. Jones, T. A.; Zou, J. Y.; Cowan, S. W.; Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 1991, 47, 110-119.
27. Wurtz, J. M.; Guillot, B.; Fagart, J.; Moras, D.; Tietjen, K.; Schindler, M. A new model for 20-hydroxyecdysone and dibenzoylhydrazine binding: a homology modeling and docking approach. Protein Sci. 2000, 9, 1073-1084.