Vitamin D receptor agonists: Opportunities and challenges in drug discovery

Current Topics in Medicinal Chemistry

Volumn 6, Issue 12, 2006, Pages 1303-1316

  Takahashi, Tadakatsu ^a   Morikawa, Kazumi ^a  

^a CHUGAI PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Nuclear receptor; Vitamin D; Vitamin D receptor (VDR)

Indexed keywords

16 ENE 22 OXAVITAMIN D DERIVATIVE; 2 METHYLENE 19 NORCALCITRIOL; 22 OXACALCITRIOL; 24 SULFONE DERIVATIVE; 24 SULFOXINE DERIVATIVE; 2BETA (3 HYDROXYPROPOXY)CALCITRIOL; ANDROSTANOLONE; BXL 628; CALCIPOTRIOL; CALCITRIOL; CALCITRIOL DERIVATIVE; CALCIUM; CD 4409; CD 4420; CYTOKINE; DOXERCALCIFEROL; FALECALCITRIOL; FINASTERIDE; LG 190178; LITHOCHOLIC ACID; OXYGENASE; PARATHYROID HORMONE; PARICALCITOL; PHOSPHORUS; PLACEBO; TACALCITOL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR; VITAMIN D RECEPTOR AGONIST;

AUTOIMMUNE DISEASE; BONE; CALCIUM METABOLISM; CLINICAL TRIAL; DRUG HALF LIFE; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; HORMONE ACTION; HUMAN; HYPERCALCEMIA; HYPERCALCIURIA; IMMUNOMODULATION; KIDNEY; NONHUMAN; OSTEOPOROSIS; PHOSPHATE METABOLISM; PROSTATE HYPERTROPHY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PSORIASIS; REGULATORY MECHANISM; REVIEW; SECONDARY HYPERPARATHYROIDISM; SMALL INTESTINE; TISSUE DISTRIBUTION; VITAMIN SUPPLEMENTATION;

DRUG DESIGN; HUMANS; HYPERPARATHYROIDISM, SECONDARY; OSTEOPOROSIS; PSORIASIS; RECEPTORS, CALCITRIOL; VITAMIN D;

EID: 33746339987     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802606777864917     Document Type: Review

References (118)

1. Bouillon, R.; Okamura W. H.; Norman, A. W. Structure-function relationships in the vitamin D endocrine system. Endocrine Rev. 1995, 16(2),200-257.
2. Omdahl, J. L.; Morris, H. A.; May, B. K. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annu. Rev. Nutr. 2002,22,139-166.
3. Akiyoshi-Shibata, M.; Sakaki, T.; Ohyama, Y.; Noshiro, M.; Okuda, K.; Yabusaki, Y. Further oxidation of hydroxycalcidiol by calcidiol 24-hydroxylase. A study with the mature enzyme expressed in Escherichia coli. Eur. J Biochem. 1994, 224(2), 335-343.
4. 3-24-hydroxylase, a multicatalytic enzyme. Biochemistry 1996, 35(25), 8465-8472.
5. 3 catalyzed by human CYP24. Eur. J. Biochem. 2000, 267(20), 6158-6165.
6. Dusso, A. S.; Brown, A. J.; Slatopolsky, E. Vitamin D. Am. J Physiol. 2005,289(1, Pt. 2), F8-F28.
7. 3-dependent cell-free transcription. Mol. Cell. Biol. 1997, 17(4), 1923-1937.
8. Blanco, J. C.; Wang, I. M.; Tsai, S. Y.; Tsai, M. J.; O'Malley, B. W.; Jurutka, P. W.; Haussler, M. R.; Ozato, K. Transcription factor TFIIB and the vitamin D receptor cooperatively activate ligand-dependent transcription. Proc. Natl. Acad. Sci. USA 1995, 92(5), 1535-1539.
9. Masuyama, H.; Brownfield, C. M.; St-Arnaud, R.; MacDonald, P. N. Evidence for ligand-dependent intramolecular folding of the AF-2 domain in vitamin D receptor-activated transcription and coactivator interaction. Mol. Endocrinol. 1997, 11(10), 1507-1517.
10. 3, and thyroid hormone receptors in mammalian cells. Genes Dev. 1997,11(11), 1381-1395.
11. Pike, J. W.; Shevde, N. K. The vitamin D receptor. Vitamin D (2nd Edition) 2005, 1, 167-191.
12. 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(1), 173-179.
13. 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(4),971-979.
14. Tocchini-Valentini, G.; Rochel, N.; Wurtz, J.-M.; Moras, D. Crystal Structures of the Vitamin D Nuclear Receptor Liganded with the Vitamin D Side Chain Analogs 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. J. Med. Chem. 2004, 47(8), 1956-1961.
15. Eelen, G.; Verlinden, L.; Rochel, N.; Claessens, F.; De Clercq, P.; Vandewalle, M.; Tocchini-Valentini, G.; Moras, D.; Bouillon, R.; Verstuyf, A. Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D explained by vitamin D receptor-coactivator interaction. Mol. Pharmacol. 2005, 67(5),1566-1573.
16. 3. Med J Osaka Univ. 1985, 35 (3-4), 51-54.
17. 3 analogs. Chem. Pharm. Bull. 1986, 34(10), 4410-4413.
18. Binderup, L.; Bramm, E. Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo. Biochem. Pharmacol. 1988, 37(5), 889-895.
19. Morisaki, M.; Koizumi, N.; Ikekawa, N.; Takeshita, T.; Ishimoto, S. Synthesis of active forms of vitamin D. Part IX Synthesis of 1α, 24-dihydroxycholecalciferol. J. Chem. Soc. Perkin Trans. 1 1975, 14,1421-1424.
20. 3 on the morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown in serum-free conditions. J. Invest Dermatol. 1986, 86(6), 709-714.
21. 3. Endocrinology 1983, 113(6), 1950-1957.
22. 3. Biochem. Pharmacol. 1995, 49(5), 621-624.
23. Lehmann, B.; Querings, K.; Reichrath, J. Vitamin D and skin: new aspects for dermatology. Exp. Dermatol. 2004, 13(Suppl. 4), 11-15.
24. 3 as pluripotent immunomodulators. J. Cellular Biochem. 2003, 88(2),223-226.
25. Kragballe, K. Treatment of psoriasis by the topical application of the novel cholecalciferol analogue calcipotriol (MC 903). Arch. Dermatol. 1989, 125(12), 1647-1652.
26. Bourke, J. F.; Berth-Jones, J.; Iqbal, S. J.; Hutchinson, P. E. High-dose topical calcipotriol in the treatment of extensive psoriasis vulgaris. Br. J Dermatol. 1993, 129(1), 74-76.
27. Bourke, J. F.; Mumford, R.; Whittaker, P.; Iqbal, S. J.; Le Van, L. W.; Trevellyan, A.; Hutchinson, P. E. The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J. Am. Acad. Dermatol. 1997, 37(6), 929-934.
28. Russell, S.; Young, M. J. Hypercalcaemia during treatment of psoriasis with calcipotriol. Br. J Dermatol. 1994, 130(6): 795-796.
29. 3 on human mesangial cells. Am. J. Kidney Dis. 1991, 18(3), 359-366.
30. Makibayashi, K.; Tatematsu, M.; Hirata, M.; Fukushima, N.; Kusano, K.; Ohashi, S.; Abe, H.; Kuze, K.; Fukatsu, A.; Kita, T.; Doi, T. A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis. Am. J. Pathol. 2001, 158(5), 1733-1741.
31. 3 on glomerulosclerosis in subtotally nephrectomized rats. Kidney Int. 1998, 53(6), 1696-1705.
32. Hirata, M.; Malkibayashi, K.; Katsumata, K.; Kusano, K.; Watanabe, T.; Fukushima, N.; Doi, T. 22-Oxacalcitriol prevents progressive glomerulosclerosis without adversely affecting calcium and phosphorus metabolism in subtotally nephrectomized rats. Nephrol. Dial. Transplant. 2002, 17(12), 2132-2137.
33. 3 is a negative endocrine regulator of the renin-angiotensin system. J. Clin. Invest. 2002, 110(2), 229-238.
34. Teng, M.; Wolf, M.; Ofsthun, M. N.; Lazarus, J. M.; Hernan, M. A.; Camargo, C. A. Jr.; Thadhani, R. Activated injectable vitamin D and hemodialysis survival: A historical cohort study. J. Am. Soc. Nephrol. 2005, 16(4),1115-1125.
35. 3 and calcium to prevent hip fractures in the elderly women. New Eng. J. Med. 1992, 327(23), 1637-1642.
36. Dawson-Hughes, B.; Harris, S. S.; Krall, E. A.; Dallal, G. E. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. New Eng. J. Med. 1997, 337(10), 670-676.
37. Bischoff-Ferrari, H. A.; Willett, W. C.; Wong, J. B.; Giovannucci, E.; Dietrich, T.; Dawson-Hughes, B. Fracture prevention with vitamin D supplementation. A meta-analysis of randomized controlled trials. J. Am. Med. Assoc. 2005,293(18),2257-2264.
38. Endo, I.; Inoue, D.; Mitsui, T.; Umaki, Y.; Akaike, M.; Yoshizawa, T.; Kato, S.; Matsumoto, T. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 2003, 144(12), 5138-5144.
39. Bischoff-Ferrari, H. A.; Borchers, M.; Gudat, F.; Duermueller, U.; Staehelin, H. B.; Dick, W. Vitamin D receptor expression in human muscle tissue decreases with age. J. Bone Miner. Res. 2004, 19(2), 265-269.
40. Tilyard, M. W.; Spears, G. F.; Thomson, J.; Dovey, S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. New Eng. J. Med. 1992,326(6),357-362.
41. Nakamura, T. Vitamin D for the treatment of osteoporosis. Osteoporosis Int. 1997, 7(Suppl. 3), 155-158.
42. Tanizawa, T.; Imura, K.; Ishii, Y.; Nishida, S.; Takano, Y.; Mashiba, T.; Endo, N.; Takahashi, H. E. Treatment with active vitamin D metabolites and concurrent treatments in the prevention of hip fractures: a retrospective study. Osteoporosis Int. 1999, 9(2), 163-170.
43. Yasuda, H.; Shima, N.; Nakagawa, N.; Yamaguchi, K.; Kinosaki, M.; Mochizuki, S.; Tomoyasu, A.; Yano, K.; Goto, M.; Murakami, A.; Tsuda, E.; Morinaga, T.; Higashio, K.; Udagawa, N.; Takahashi, N.; Suda, T. Osteoclast differentiation factor is a ligand for osteoprotegerin/ osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl. Acad. Sci. USA 1998, 95(7), 3597-3602.
44. 3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women. Bone 1997, 20(6), 557-562.
45. Shibata, T.; Shira-Ishi, A.; Sato, T.; Masaki, T.; Sasaki, A.; Masuda, Y.; Hishiya, A.; Ishikura, N.; Higashi, S.; Uchida, Y.; Saito, M.-O.; Ito, M.; Ogata, E.; Watanabe, K.; Ikeda, K. Vitamin D hormone inhibits osteoclastogenesis in vivo by decreasing the pool of osteoclast precursors in bone marrow. J. Bone Miner. Res. 2002, 17(4), 622-629.
46. Shiraishi, A.; Higashi, S.; Masaki, T.; Saito, M.; Ito, M.; Ikeda, S.; Nakamura, T. A Comparison of Alfacalcidol and Menatetrenone for the Treatment of Bone Loss in an Ovariectomized Rat Model of Osteoporosis. Calcif Tis. Int. 2002, 71(1), 69-79.
47. Shiraishi, A.; Takeda, S.; Masaki, T.; Higuchi, Y.; Uchiyama, Y.; Kubodera, N.; Sato, K.; Ikeda, K.; Nakamura, T.; Matsumoto, T.; Ogata, E. Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen. J. Bone Miner. Res. 2000, 15(4), 770-779.
48. Li, M.; Li, Y.; Healy, D. R.; Simmons, H. A.; Ke, H. Z.; Thompson, D. D. Alfacalcidol restores cancellous bone in ovariectomized rats. J. Musculaskel. Neuron. Interact 2003, 3(1), 39-46.
49. 3 acts as a bone-forming agent in the hormone-independent senescence-accelerated mouse (SAM-P/6). Am. J. Physiol. 2005, 288(4, Pt. 1), E723-E730.
50. 3. J. Bone Miner. Res. 2002, 17(8), 1498-1511.
51. 3 as modulators in the immune system. J. Steroid Biochem. Mol. Biol. 2004,89-90(1-5),449-452.
52. Hewison, M.; Freeman, L.; Hughes, S. V.; Evans, K. N.; Bland, R.; Eliopoulos, A. G.; Kilby, M. D.; Moss, P. A. H.; Chakraverty, R. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J. Immunol. 2003, 170(11),5382-5390.
53. 3-mediated effects. J. Immunol. 1998,160(1), 209-218.
54. 3: a transcriptional modulator of the interferon-γ gene. Eur. J. Immunol. 1998, 28(10), 3017-3030.
55. 3 induces an autoantigen-specific T-helper 1/ T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543). Diabetes 2000, 49(8), 1301-1307.
56. 3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol. 2001, 167(9), 4974-4980.
57. Adorini, L. Intervention in autoimmunity: The potential of vitamin D receptor agonists. Cell. Immunol. 2005, 233(2), 115-124.
58. 3 in rheumatoid arthritis patients. Clin. Exp. Rheuimatol 1999, 17(4), 453-456.
59. 3: a pilot study. Arthritis Rheum. 1990, 33(11),1723-1727.
60. Garland, C. F.; Garland, F. C. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int. J. Epidemiol. 1980, 9(3),227-231.
61. Garland, C. F.; Comstock, G. W.; Garland, F. C.; Helsing, K. J.; Shaw, E. K.; Gorham, E. D. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 1989, 2(8673), 1176-1178.
62. Walters, M. R. Newly identified actions of the vitamin D endocrine system. Endocrine Rev. 1992, 13(4), 719-764.
63. Hartwell, L. H.; Kastan, M. B. Cell cycle control and cancer. Science 1994, 266(5192), 1821-1828.
64. Sherr, C. J.; Roberts, J. M. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995, 9(10), 1149-1163.
65. 3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996,10(2),142-153.
66. 3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7 cells. Mol. Cell. Endocrinol. 1998, 142(1-2), 57-65.
67. 3 and its analogs inhibit acute myelogenous leukemia progenitor proliferation by suppressing interleukin-1β production. J. Clin. Invest. 1997, 100(7),1716-1724.
68. 3 analog-induced growth inhibition in breast cells. J. Cell. Physiol 2001, 188(3), 383-393.
69. Guyton Kathryn, Z.; Kensler Thomas, W.; Posner Gary, H. Vitamin D and vitamin D analogs as cancer chemopreventive agents. Nutrition Rev. 2003, 61(7), 227-238.
70. Scardino Peter, T. The prevention of prostate cancer-the dilemma continues. New Eng. J. Med. 2003, 349(3), 297-299.
71. Hieble, J. P. Therapeutic strategies for benign prostatic hypertrophy. Drug Discov. Today: Therapeutic Strategies 2004, 1(2), 243-248.
72. 3 on primary cultures of human prostatic cells. Cancer Res. 1994, 54(3), 805-810.
73. Konety, B. R.; Leman, E.; Vietmeier, B.; Arlotti, J.; Dhir, R.; Getzenberg, R. H. In vitro and in vivo effects of vitamin D (calcitriol) administration on the normal neonatal and prepubertal prostate. J. Urology 2000, 164(5), 1812-1818.
74. Krill, D.; Stoner, J.; Konety, B. R.; Becich, M. J.; Getzenberg, R. H. Differential effects of vitamin D on normal human prostate epithelial and stromal cells in primary culture. Urology 1999, 54(1),171-177.
75. Crescioli, C.; Ferruzzi, P.; Caporali, A.; Mancina, R.; Comerci, A.; Muratori, M.; Scaltriti, M.; Vannelli, G. B.; Smiroldo, S.; Mariani, R.; Villari, D.; Bettuzzi, S.; Setio, M.; Adorini, L.; Maggi, M. Inhibition of spontaneous and androgen-induced prostate growth by a nonhypercalcemic calcitriol analog. Endocrinology 2003, 144(7), 3046-3057.
76. Posner, G. H.; Kahraman, M. Organic chemistry of vitamin D analogs (deltanoids). Eur. J. Org. Chem. 2003(20), 3889-3895.
77. Pinette Karen, V.; Yee Ying, K.; Amegadzie Bernard, Y.; Nagpal, S. Vitamin D receptor as a drug discovery target. Mini Rev. Med. Chem. 2003, 3(3), 193-204.
78. Yamada, S.; Shimizu, M.; Yamamoto, K. Structure-function relationships of vitamin D including ligand recognition by the vitamin D receptor. Med. Res. Rev. 2003, 23(1), 89-115.
79. 3 analogs bearing a hydroxyalkoxy group at the 2 β-position. Chem. Pharm. Bull. 1993, 41(6),1111-1113.
80. 3 analogs substituted at the 2β-position and their preventive effects on bone mineral loss in ovariectomized rats. Chem. Pharm. Bull. 1997, 45(10), 1626-1630.
81. 3 (ED-71) on bone mineral loss in ovariectomized rats. Bioorg. Med. Chem. 1998, 6(12),2517-2523.
82. Kubodera; N.; Tsuji, N.; Uchiyama, Y.; Endo, K. A new active vitamin D analog, ED-71, causes increase in bone mass with preferential effects on bone in osteoporotic patients. J. Cellular Biochem. 2003, 88(2), 286-289.
83. Uchiyama, Y.; Higuchi, Y.; Takeda, S.; Masaki, T.; Shira-ishi, A.; Sato, K.; Kubodera, N.; Ikeda, K.; Ogata, E. ED-71, a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis. Bone 2002, 30(4), 582-588.
84. Tanaka, Y.; Nakamura, T.; Nishida, S.; Suzuki, K.; Takeda, S.; Sato, K.; Nishii, Y. Effects of a synthetic vitamin D analog, ED-71, on bone dynamics and strength in cancellous and cortical bone in prednisolone-treated rats. J. Bone Miner. Res. 1996, 11(3), 325-336.
85. Matsumoto, T.; Miki, T.; Hagino, H.; Sugimoto, T.; Okamoto, S.; Hirota, T.; Tanigawara, Y.; Hayashi, Y.; Fukunaga, M.; Shiraki, M.; Nakamura, T. A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: A randomized, double-blind, placebo-controlled clinical trial. J. Clin. Endocrinol. Metab. 2005,90(9),5031-5036.
86. 3 Compounds of High Biological Activity: Synthesis and Biological Evaluation of 2-Hydroxymethyl, 2-Methyl, and 2-Methylene Analogs. J. Med. Chem. 1998,41(23),4662-4674.
87. 3 selectively induces bone formation. Proc. Natl. Acad. Sci. USA 2002, 99(21), 13487-13491.
88. 3: synthesis, biological activities and docking to the ligand binding domain of die rat vitamin D receptor. J. Steroid Biochem. Mol. Biol. 2004, 89-90(1-5), 13-17.
89. Crescioli, C.; Ferruzzi, P.; Caporali, A.; Scaltriti, M.; Bettuzzi, S.; Mancina, R.; Gelmini, S.; Serio, M.; Villari, D.; Vannelli, G. B.; Colli, E.; Adorini, L.; Maggi, M. Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia. Eur. J. Endocrinol. 2004, 150(4), 591-603.
90. Brown, A. J.; Finch, J.; Grieff, M.; Ritter, C.; Kubodera, N.; Nishii, Y.; Slatopolsky, E. The mechanism for the disparate actions of calcitriol and 22-oxacalcitriol in the intestine. Endocrinology 1993, 133(3),1158-64.
91. Masuda, S.; Byford, V.; Kremer, R.; Makin, H. L. J.; Kubodera, N.; Nishii, Y.; Okazaki, A.; Okano, T.; Kobayashi, T.; Jones, G. In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines. J. Biol. Chem. 1996, 271(15), 8700-8708.
92. 3 analogs: a novel class of potent regulators of cell growth and immune responses. Biochem. Pharmacol. 1991, 42(8), 1569-1575.
93. 3. Biochem. Pharmacol. 1991, 41(11), 1601-1606.
94. Kissmeyer, A. M.; Mathiasen, I. S.; Latini, S.; Binderup, L. Pharmacokinetic studies of vitamin D analogs: relationship to vitamin D binding protein (DBP). Endocrine 1995, 3(4), 263-266.
95. 3 Analogs. Bioorg. Med. Chem. 2005, in press.
96. 3. J. Steroid Biochem. Mol. Biol. 2004, 89-90(1-5), 5-12.
97. 3. J. Med. Chem. 2004, 47(27), 6854-6863.
98. Plum, L. A.; Prahl, J. M.; Ma, X.; Sicinski, R. R.; Gowlugari, S.; Clagett-Dame, M.; DeLuca, H. F. Biologically active noncalcemic analogs of 1α,25-dihydroxyvitamin D with an abbreviated side chain containing no hydroxyl. Proc. Natl. Acad. Sci. USA 2004, 101(18), 6900-6904.
99. 3 receptor. J. Steroid Biochem. Mol. Biol. 2005, 94(4), 279-288.
100. 3) Induce Vitamin D Receptor Transcriptional Activity. Org. Left. 2003, 5(22),4033-4036.
101. 3 reduces secondary hyperparathyroidism in uremic rats with little calcemic effect. Horm. Res. 2004, 61(1), 7-16.
102. 3 derivatives in quest of a drug with low calcemic activity. Tetrahedron Lett. 2004, 45(42), 7837-7841.
103. 3 with a trans-fused decalin CD-ring has pronounced genomic activity. J. Biol. Chem. 2003, 278(37), 35476-35482.
104. Chen, Y.-J.; Gao, L.-J.; Murad, I.; Verstuyf, A.; Verlinden, L.; Verboven, C.; Bouillon, R.; Viterbo, D.; Milanesio, M.; Van Haver, D.; Vandewalle, M.; De Clercq, P. J. Synthesis, biological activity, and conformational analysis of CD-ring modified trans-decalin 1α,25-dihydroxyvitamin D analogs. Org. Biomol. Chem. 2003, 1(2), 257-267.
105. 3 Strongly Modulates the Affinity for the Vitamin D Receptor (VDR). Org. Lett. 2003, 5(13), 2291-2293.
106. 3 Analogs, Including 2-epi-ED-71 and Their 20-Epimers with HL-60 Cell Differentiation Activity. J. Org. Chem. 2004, 69(22), 7463-7471.
107. Makishima, M.; Lu, T. T.; Xie, W.; Whitfield, G. K.; Domoto, H.; Evans, R. M.; Haussler, M. R.; Mangelsdorf, D. J. Vitamin D receptor as an intestinal bile acid sensor. Science 2002, 296(5571), 1313-1316.
108. Adachi, R.; Honma, Y.; Masuno, H.; Kawana, K.; Shimomura, I.; Yamada, S.; Makishima, M. Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative. J. Lipid. Res. 2005,46(1), 46-57.
109. Sun, J.; Meyers, M. J.; Fink, B. E.; Rajendran, R.; Katzenellenbogen, J. A.; Katzenellenbogen, B. S. Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-α or estrogen receptor-β. Endocrinology 1999, 140(2), 800-804.
110. Yin, D.; He, Y.; Perera, M. A.; Hong, S. S.; Marhefka, C.; Stourman, N.; Kirkovsky, L.; Miller, D. D.; Dalton, J. T. Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor. Mol. Pharmarol. 2003, 63(1), 211-223.
111. Einstein, M.; Greenlee, M.; Rouen, G.; Sitlani, A.; Santoro, J.; Wang, C.; Pandit, S.; Mazur, P.; Smalera, I.; Weaver, A. P. M.; Zeng, Y. Y.; Ge, L.; Kelly, T.; Paiva, T.; Geissler, W.; Mosley, R. T.; Williamson, J.; Ali, A.; Balkovec, J.; Harris, G. Selective glucocorticoid receptor nonsterindal ligands completely antagonize the dexamethasone mediated induction of enzymes involved in gluconeogenesis and glutamine metabolism. J. Steroid Biochem. Mol. Biol. 2004, 92(5),345-356.
112. 3. Chem. Biol. 1999, 6(5), 265-275.
113. Swann, S. L.; Bergh, J.; Farach-Carson, M. C.; Ocasio, C. A.; Koh, J. T. Structure-Based Design of Selective Agonists for a Rickets-Associated Mutant of the Vitamin D Receptor. J. Am. Chem. Soc. 2002, 124(46), 13795-13805.
114. Polek, T. C.; Murthy, S.; Blutt, S. E.; Boehm, M. F.; Zou, A.; Weigel, N. L.; Allegretto, E. A. Novel nonsecosteroidal vitamin D receptor modulator inhibits the growth of LNCaP xenograft tumors in athymic mice without increased serum calcium. Prostate 2001, 49(3), 224-233.
115. Peraekylae, M.; Malinen, M.; Herzig, K.-H.; Carlberg, C. Gene regulatory potential of nonsteroidal vitamin D receptor ligands. Mol. Endocrinol. 2005, 19(8), 2060-2073.
116. Teramoto, T.; Endo, K.; Ikeda, K.; Kubodera, N.; Kinoshita, M.; Yamanaka, M.; Ogata, E. Binding of vitamin D to low-density-lipoprotein (LDL) and LDL receptor-mediated pathway into cells. Biochem. Biophys. Res. Comm. 1995, 215(1),199-204.
117. Takeyama, K.; Masuhiro, Y.; Fuse, H.; Endoh, H.; Murayama, A.; Kitanaka, S.; Suzawa, M.; Yanagisawa, J.; Kato, S. Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog. Mol. Cell. Biol. 1999, 19(2),1049-1055.
118. Kitagawa, H.; Fujiki, R.; Yoshimura, K.; Mezaki, Y.; Uematsu, Y.; Matsui, D.; Ogawa, S.; Unno, K.; Okubo, M.; Tokita, A.; Nakagawa, T.; Ito, T.; Ishimi, Y.; Nagasawa, H.; Matsumoto, T.; Yanagisawa, J.; Kato, S. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell 2003, 113(7), 905-917.