Therapeutic applications for novel non-hypercalcemic vitamin D receptor ligands

Expert Opinion on Therapeutic Patents

Volumn 19, Issue 5, 2009, Pages 593-606

  Choi, Mihwa ^a   Makishima, Makoto ^a  

^a NIHON UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Autoimmune disease; Bile acid; Cancer; Hypercalcemia; Infection; Osteoporosis; Parathyroid hormone; Vitamin D; Vitamin D receptor

Indexed keywords

1,25 DIHYDROXY 21 (3 HYDROXY 3 TRIFLUOROMETHYL 4 TRIFLUORO BUTYNYL) 26,27 HEXADEUTERO 19 NORCHOLECALCIFEROL; 1,3,24 TRIHYDROXY 26,27 CYCLO 9,10 SECOCHOLESTA 5,7,10(19),22 TETRAENE 25 CARBOXYLIC ACID BUTYL ESTER; 1ALPHA FLUORO 25 HYDROXYDIENE 26,27 BISHOMO 20 EPICHOLECALCIFEROL; 1ALPHA HYDROXY 25,27 DIDEHYDROVITAMIN D3 26,23 LACTONE; 1ALPHA,24 DIHYDROXY 25 (ETHOXYACRYLO 3 YL) 26,27 CYCLO 22,23 DIDEHYDROVITAMIN D3; 2 MD; 2 METHYLENE 19 NOR 1ALPHA HYDROXYBISHOMOPREGNACALCIFEROL; 2 METHYLENE 19 NOR 1ALPHA,25 DIHYDROXYVITAMIN D3; 22 OXACALCITRIOL; 25 (BUTOXYCARBONYL) 1ALPHA,24 DIHYDROXY 26,27 CYCLO 22,23 DIDEHYDROVITAMIN D3; 2BETA (3 HYDROXYPROPOXY)CALCITRIOL; ALFACALCIDOL; BXL 010072; CALCIPOTRIOL; CALCITRIOL; CD 4528; DOXERCALCIFEROL; FALECALCITRIOL; GEMINI; LIGAND; LITHOCHOLIC ACID ACETATE; LITHOCHOLIC ACID PROPIOATE; LY 2108491; LY 2109866; LY 2109886; PARICALCITOL; RO 269228; TACALCITOL; TIE 9647; UNCLASSIFIED DRUG; VITAMIN D; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR; VITAMIN D RECEPTOR LIGAND; WATER OIL CREAM; ZK 168281;

ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; BONE DEVELOPMENT; COLON TUMOR; DOSE RESPONSE; DRUG CLEARANCE; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HUMAN; LUPUS ERYTHEMATOSUS NEPHRITIS; NONHUMAN; OSTEOPOROSIS; PATENT; PSORIASIS; REVIEW; SECONDARY HYPERPARATHYROIDISM; SKIN IRRITATION; VITAMIN D DEFICIENCY;

ANIMALS; CALCITRIOL; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; LIGANDS; PATENTS AS TOPIC; RECEPTORS, CALCITRIOL; VITAMIN D;

EID: 67649366435     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543770902877717     Document Type: Review

References (69)

1. Holick MF. Vitamin D Deficiency. N Engl J Med 2007;357:266-281 •• Excellent review on vitamin D deficiency.
2. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004;80:1689S-96S •• Excellent review on vitamin D deficiency.
3. Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005;26:662-687 •• Excellent review on the medical application of VDR ligands. (Pubitemid 41127276)
4. Makishima M, Yamada S. Targeting the vitamin D receptor: advances in drug discovery. Expert Opin Ther Pat 2005;15:1133-1145 • Our previous review on VDR ligands. (Pubitemid 41358432)
5. Makishima M. Nuclear receptors as targets for drug development: regulation of cholesterol and bile acid metabolism by nuclear receptors. J Pharmacol Sci 2005;97:177-183 • Our review on nuclear receptors and lipid metabolism. (Pubitemid 40410256)
6. Rosenfeld MG, Lunyak VV, Glass CK. Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes Dev 2006;20:1405-1428 •• Excellent review on nuclear receptor cofactors. (Pubitemid 43830648)
7. Kim MS, Fujiki R, Kitagawa H, Kato S. 1α,25(OH)2D3-induced DNA methylation suppresses the human CYP27B1 gene. Mol Cell Endocrinol 2007;265-266:168-173 • Review on VDR transrepression. (Pubitemid 46273961)
8. Kato S, Fujiki R, Kim MS, Kitagawa H. Ligand-induced transrepressive function of VDR requires a chromatin remodeling complex, WINAC. J Steroid Biochem Mol Biol 2007;103:372-380 (Pubitemid 46401329)
9. Carlberg C, Dunlop TW, Saramaki A, et al. Controlling the chromatin organization of vitamin D target genes by multiple vitamin D receptor binding sites. J Steroid Biochem Mol Biol 2007;103:338-343 (Pubitemid 46401335)
10. Haussler MR, Whitfield GK, Haussler CA, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325-349 •• Excellent review on VDR biology. (Pubitemid 28146215)
11. Thummel KE, Brimer C, Yasuda K, et al. Transcriptional control of intestinal cytochrome P-4503A by 1α,25-dihydroxy vitamin D3. Mol Pharmacol 2001;60:1399-1406 (Pubitemid 33144911)
12. Saramaki A, Banwell CM, Campbell MJ, Carlberg C. Regulation of the human p21(waf1/cip1) gene promoter via multiple binding sites for p53 and the vitamin D3 receptor. Nucl Acids Res 2006;34:543-554 (Pubitemid 43240242)
13. Sinkkonen L, Malinen M, Saavalainen K, et al. Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter. Nucl Acids Res 2005;33:2440-2451 (Pubitemid 41511263)
14. Matilainen M, Malinen M, Saavalainen K, Carlberg C. Regulation of multiple insulin-like growth factor binding protein genes by 1α,25-dihydroxyvitamin D3. Nucl Acids Res 2005;33:5521-5532 (Pubitemid 41548818)
15. Kim MS, Fujiki R, Murayama A, et al. 1α,25(OH)2D3-induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter. Mol Endocrinol 2007;21:334-342 (Pubitemid 46188281)
16. Brown AJ, Dusso AS, Slatopolsky E. Vitamin D analogues for secondary hyperparathyroidism. Nephrol Dial Transplant 2002;17:10-19 •• Excellent review on VDR ligands and secondary hyperparathyroidism. (Pubitemid 35277070)
17. Carlberg C. Molecular basis of the selective activity of vitamin D analogues. J Cell Biochem 2003;88:274-281 • Excellent review on vitamin D derivatives. (Pubitemid 36119898)
18. Makishima M, Lu TT, Xie W, et al. Vitamin D receptor as an intestinal bile acid sensor. Science 2002;296:1313-1316 (Pubitemid 34522785)
19. Okano T, Tsugawa N, Masuda S, et al. Regulatory activities of 2β-(3-hydroxypropoxy)-1α, 25-dihydroxyvitamin D3, a novel synthetic vitamin D3 derivative, on calcium metabolism. Biochem Biophys Res Commun 1989;163:1444-1449 (Pubitemid 19244750)
20. Okano T, Tsugawa N, Masuda S, et al. Protein-binding properties of 22-oxa-1α,25-dihydroxyvitamin D3, a synthetic analogue of 1α,25-dihydroxyvitamin D3. J Nutr Sci Vitaminol 1989;35:529-533 (Pubitemid 20101820)
21. Brown AJ, Finch J, Grieff M, et al. The mechanism for the disparate actions of calcitriol and 22-oxacalcitriol in the intestine. Endocrinology 1993;133:1158-1164 (Pubitemid 23267767)
22. Choi M, Yamamoto K, Itoh T, et al. Interaction between vitamin D receptor and vitamin D ligands: two-dimensional alanine scanning Mutational Analysis. Chem Biol 2003;10:261-270 (Pubitemid 36380283)
23. Takeyama K, Masuhiro Y, Fuse H, et al. Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog. Mol Cell Biol 1999;19:1049-1055 (Pubitemid 29046848)
24. Abe J, Nakamura K, Takita Y, et al. Prevention of immunological disorders in MRL/l mice by a new synthetic analogue of vitamin D3: 22-oxa-1α,25- dihydroxyvitamin D3. J Nutr Sci Vitaminol 1990;36:21-31 (Pubitemid 20200284)
25. Koike N, Hayakawa N, Tokuda K, et al. In vivo time-course of receptor binding in the parathyroid gland of the vitamin D analogue [3H]1, 25-dihydroxy-22-oxavitamin D3 compared with [3H]1,25-dihydroxyvitamin D3, determined by micro-autoradiography. Nephrol Dial Transplant 2002;17:53-57
26. Li M, Hener P, Zhang Z, et al. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci USA 2006;103:11736-11741 (Pubitemid 44182520)
27. Sprague SM, Llach F, Amdahl M, et al. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 2003;63:1483-1490 (Pubitemid 36350014)
28. Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342:1478-1483 (Pubitemid 30318271)
29. Teng M, Wolf M, Lowrie E, et al. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003;349:446-456 (Pubitemid 36910023)
30. Kumagai T, O'Kelly J, Said JW, Koeffler HP. Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. J Natl Cancer Inst 2003;95:896-905 (Pubitemid 36833881)
31. Tanaka Y, Nakamura T, Nishida S, et al. 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;11:325-336 (Pubitemid 26076382)
32. Okuda N, Takeda S, Shinomiya K, et al. ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation. Bone 2007;40:281-292 (Pubitemid 46075203)
33. 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 Cell Biochem 2003;88:286-289 (Pubitemid 36119900)
34. Matsumoto T, Miki T, Hagino H, et al. 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;90:5031-5036 (Pubitemid 41262250)
35. Sicinski RR, Prahl JM, Smith CM, Deluca HF. New 1α,25-dihydroxy-19- norvitamin D3 compounds of high biological activity: synthesis and biological evaluation of 2-hydroxymethyl, 2-methyl, and 2-methylene analogues. J Med Chem 1998;41:4662-4674 (Pubitemid 28516465)
36. Shevde NK, Plum LA, Clagett-Dame M, et al. A potent analog of 1α,25-dihydroxyvitamin D3 selectively induces bone formation. Proc Natl Acad Sci USA 2002;99:13487-13491 (Pubitemid 35215408)
37. Thomson B, Ahrens JM, Ntambi JM, et al. 2-Methylene-19-nor-1α- hydroxyvitamin D3 analogs inhibit adipocyte differentiation and PPARγ2 gene transcription. Arch Biochem Biophys 2007;460:192-201 (Pubitemid 46589398)
38. Schwinn MK, DeLuca HF. Differential recruitment of coactivators to the vitamin D receptor transcriptional complex by 1α,25-dihydroxyvitamin D3 analogs. Arch Biochem Biophys 2007;465:443-451 (Pubitemid 47362002)
39. Vanhooke JL, Benning MM, Bauer CB, et al. Molecular structure of the rat vitamin D receptor ligand binding domain complexed with 2-carbon-substituted vitamin D3 hormone analogues and a LXXLL-containing coactivator peptide. Biochemistry 2004;43:4101-4110 (Pubitemid 38445629)
40. Yamamoto H, Shevde NK, Warrier A, et al. 2-Methylene-19-nor-(20S)-1,25- dihydroxyvitamin D3 potently stimulates gene-specific DNA binding of the vitamin D receptor in osteoblasts. J Biol Chem 2003;278:31756-31765 (Pubitemid 37048356)
41. Plum LA, Prahl JM, Ma X, et al. Biologically active noncalcemic analogs of 1α,25-dihydroxyvitamin D with an abbreviated side chain containing no hydroxyl. Proc Natl Acad Sci USA 2004;101:6900-6904 (Pubitemid 38596415)
42. Williams KB, DeLuca HF. 2-Methylene-19-nor-20(S)-1α- hydroxybishomopregnacalciferol [20(S)-2MbisP], an analog of vitamin D3 [1,25(OH)2D3], does not stimulate intestinal phosphate absorption at levels previously shown to suppress parathyroid hormone. Steroids 2008;73:1277-1284
43. Slatopolsky E, Finch JL, Brown AJ, et al. Effect of 2-methylene-19-nor- (20S)-1α-hydroxy-bishomopregnacalciferol (2MbisP), an analog of vitamin D, on secondary hyperparathyroidism. J Bone Miner Res 2007;22:686-694 (Pubitemid 351339096)
44. Albert DM, Plum LA, Yang W, et al. Responsiveness of human retinoblastoma and neuroblastoma models to a non-calcemic 19-nor Vitamin D analog. J Steroid Biochem Mol Biol 2005;97:165-172 (Pubitemid 41546226)
45. Peleg S, Uskokovic M, Ahene A, et al. Cellular and molecular events associated with the bone-protecting activity of the noncalcemic vitamin D analog Ro-26-9228 in osteopenic rats. Endocrinology 2002;143:1625-1636 (Pubitemid 34415876)
46. Ismail A, Nguyen CV, Ahene A, et al. Effect of cellular environment on the selective activation of the vitamin D receptor by 1α,25- Dihydroxyvitamin D3 and its analog 1α-fluoro-16-ene-20-epi-23-ene-26,27- bishomo-25-hydroxyvitamin D3 (Ro-26-9228). Mol Endocrinol 2004;18:874-887 (Pubitemid 38429479)
47. Vaisanen S, Perakyla M, Karkkainen JI, et al. Structural evaluation of the agonistic action of a vitamin D analog with two side chains binding to the nuclear vitamin D receptor. Mol Pharmacol 2003;63:1230-1237 (Pubitemid 36627217)
48. Carlberg C, Mourino A. New vitamin D receptor ligands. Expert Opin Ther Pat 2003;13:761-772 • Excellent review on VDR ligands, including antagonists. (Pubitemid 36748942)
49. Norman AW, Manchand PS, Uskokovic MR, et al. Characterization of a novel analogue of 1α,25(OH)2-vitamin D3 with two side chains: interaction with its nuclear receptor and cellular actions. J Med Chem 2000;43:2719-2730 (Pubitemid 30463920)
50. Gonzalez MM, Samenfeld P, Perakyla M, Carlberg C. Corepressor excess shifts the two-side chain vitamin D analog Gemini from an agonist to an inverse agonist of the vitamin D receptor. Mol Endocrinol 2003;17:2028-2038 (Pubitemid 37281795)
51. Spina C, Tangpricha V, Yao M, et al. Colon cancer and solar ultraviolet B radiation and prevention and treatment of colon cancer in mice with vitamin D and its Gemini analogs. J Steroid Biochem Mol Biol 2005;l97:111-120 (Pubitemid 41546220)
52. Ishizuka S, Miura D, Ozono K, et al. Antagonistic actions in vivo of (23S)-25-dehydro-1α-hydroxyvitamin D3-26,23-lactone on calcium metabolism induced by 1α,25-dihydroxyvitamin D3. Endocrinology 2001;142:59-67 (Pubitemid 32183666)
53. Inaba Y, Yamamoto K, Yoshimoto N, et al. Vitamin D3 derivatives with adamantane or lactone ring side chains are cell type-selective vitamin D receptor modulators. Mol Pharmacol 2007;71:1298-1311 (Pubitemid 46658683)
54. Ma Y, Khalifa B, Yee YK, et al. Identification and characterization of noncalcemic, tissue-selective, nonsecosteroidal vitamin D receptor modulators. J Clin Invest 2006;116:892-904
55. Perakyla M, Malinen M, Herzig KH, Carlberg C. Gene regulatory potential of nonsteroidal vitamin D receptor ligands. Mol Endocrinol 2005;19:2060-2073 (Pubitemid 41124201)
56. Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 1999;159:2647-2658 • Excellent review on bile acids.
57. Adachi R, Shulman AI, Yamamoto K, et al. Structural determinants for vitamin D receptor response to endocrine and xenobiotic signals. Mol Endocrinol 2004;18:43-52 (Pubitemid 38073152)
58. Yamamoto K, Abe D, Yoshimoto N, et al. Vitamin D receptor: ligand recognition and allosteric network. J Med Chem 2006;49:1313-1324 (Pubitemid 43271885)
59. Ishizawa M, Matsunawa M, Adachi R, et al. Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. J Lipid Res 2008;49:763-772
60. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006;311:1770-1773
61. Nijenhuis T, Hoenderop JG, Bindels RJ. TRPV5 and TRPV6 in Ca(2+) (re) absorption: regulating Ca(2+) entry at the gate. Pflugers Arch 2005;451:181-192
62. Kutuzova GD, Akhter S, Christakos S, et al. Calbindin D9k knockout mice are indistinguishable from wild-type mice in phenotype and serum calcium level. Proc Natl Acad Sci USA 2006;103:12377-12381 (Pubitemid 44267267)
63. Hoenderop JGJ, van Leeuwen JPTM, van der Eerden BCJ, et al. Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest 2003;112:1906-1914 (Pubitemid 38063714)
64. Bianco SDC, Peng JB, Takanaga H, et al. Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J Bone Miner Res 2007;22:274-285 (Pubitemid 46167798)
65. Kutuzova GD, Sundersingh F, Vaughan J, et al. TRPV6 is not required for 1α,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo. Proc Natl Acad Sci USA 2008;105:19655-19659
66. Sakaki T, Sawada N, Abe D, et al. Metabolism of 26,26,26,27,27,27-F6- 1α,25-dihydroxyvitamin D3 by CYP24: species-based difference between humans and rats. Biochem Pharmacol 2003;65:1957-1965
67. Committee NRN. A unified nomenclature system for the nuclear receptor superfamily. Cell 1999;97:161-163
68. Whitfield GK, Dang HTL, Schluter SF, et al. Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth. Endocrinology 2003;144:2704-2716 (Pubitemid 36629924)
69. Nehring JA, Zierold C, DeLuca HF. Lithocholic acid can carry out in vivo functions of vitamin D. Proc Natl Acad Sci USA 2007;104:10006-10009 (Pubitemid 47175253)