Contribution of several metabolites of the vitamin D analog 20-epi-22-oxa-24a,26a,27a-tri-homo-1,25-(OH)2 vitamin D3 (KH 1060) to the overall biological activity of KH1060 by a shared mechanism of action

Biochemical Pharmacology

Volumn 59, Issue 6, 2000, Pages 621-627

  Van Den Bemd, Gert Jan C M ^a   Dilworth, F Jeffrey ^b   Makin, Hugh L J ^c   Prahl, Jean M ^d   Deluca, Hector F ^d   Jones, Glenville ^b   Pols, Huibert A P ^a   Van Leeuwen, Johannes P T M ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b QUEEN S UNIVERSITY   (Canada)

^c ST BARTHOLOMEW S HOSPITAL   (United Kingdom)

^d UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

KH1060; Metabolites; Receptor conformation; Receptor stability; Vitamin D analogs; Vitamin D receptor

Indexed keywords

CALCITRIOL; DRUG METABOLITE; LEXACALCITOL; OSTEOCALCIN; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR;

ANIMAL CELL; ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG MECHANISM; DRUG RECEPTOR BINDING; NONHUMAN; OSTEOBLAST; PRIORITY JOURNAL; PROTEIN DEGRADATION; RAT;

ANIMALS; CALCITRIOL; CALCIUM CHANNEL AGONISTS; CELLS, CULTURED; ELECTROPHORESIS, AGAR GEL; HALF-LIFE; IMMUNOSUPPRESSIVE AGENTS; OSTEOCALCIN; PEPTIDE HYDROLASES; PRODRUGS; RATS; RECEPTORS, CALCITRIOL; VITAMIN D;

EID: 0033951978     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(99)00371-8     Document Type: Article

References (31)

1. Vieth R. The mechanisms of vitamin D toxicity. Bone Miner. 11:1990;267-272.
2. Bouillon R., Okamura W.H., Norman A.W. Structure-function relationships in the vitamin D endocrine system. Endocr Rev. 16:1995;200-257.
3. 3 analogues A novel class of potent regulators of cell growth and immune responses . Biochem Pharmacol. 42:1991;1569-1575.
4. Binderup L. Immunological properties of vitamin D analogues and metabolites. Biochem Pharmacol. 43:1992;1885-1892.
5. 3 analogs and tamoxifen. Cancer Res. 54:1994;5711-5717.
6. 3-analogs on osteoblast-like cells and on in vitro bone resorption. J Steroid Biochem Mol Biol. 55:1995;337-346.
7. 3 analog KH1060. Proc Natl Acad Sci U S A. 93:1996;10685-10690.
8. Dilworth F.J., Williams G.R., Kissmeyer A.M., Nielsen J.L., Binderup E., Calverley M.J., Makin H.L., Jones G. The vitamin D analog, KH1060, is rapidly degraded both in vivo and in vitro via several pathways Principal metabolites generated retain significant biological activity . Endocrinology. 138:1997;5485-5496.
9. Verhaeghe J., Van Herck E., Van Bree R., Van Assche F.A., Bouillon R. Osteocalcin during the reproductive cycle in normal and diabetic rats. J Endocrinol. 120:1989;143-151.
10. 3 results from ligand-induced stabilization. J Biol Chem. 267:1992;20082-20086.
11. 3 receptor protein. J Bone Miner Res. 11:1996;1921-1925.
12. Baker A.R., McDonnell D.P., Hughes M., Crisp T.M., Mangelsdorf D.J., Haussler M.R., Pike J.W., Shine J., O'Malley B.W. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A. 85:1988;3294-3298.
13. Staal A., van Wijnen A.J., Birkenhäger J.C., Pols H.A., Prahl J., DeLuca H., Gaub M.P., Lian J.B., Stein G.S., van Leeuwen J.P., Stein J.L. Distinct conformations of vitamin D receptor/retinoid X receptor-alpha heterodimers are specified by dinucleotide differences in the vitamin D-responsive elements of the osteocalcin and osteopontin genes. Mol Endocrinol. 10:1996;1444-1456.
14. 3 are associated with enhanced activation of the vitamin D receptor. J Biol Chem. 270:1995;10551-10558.
15. 3 correlates well with gene activation. J Cell Biochem. 62:1996;325-333.
16. 3. Biochem Pharmacol. 45:1993;2331-2336.
17. 3 is due to reduced catabolism and altered protein binding. Biochem Pharmacol. 47:1994;987-993.
18. Kissmeyer A.M., Mathiasen I.S., Latini S., Binderup L. Pharmacokinetic studies of vitamin D analogues Relationship to vitamin D binding protein (DBP) . Endocrine. 3:1995;263-266.
19. Shankar V.N., Dilworth F.J., Makin H.L., Schroeder N.J., Trafford D.J.H., Kissmeyer A.M., Calverley M.J., Binderup E., Jones G. Metabolism of the vitamin D analog EB1089 by cultured human cells Redirection of hydroxylation site to distal carbons of the side-chain . Biochem Pharmacol. 53:1997;783-793.
20. Jones G. Analog metabolism. Feldman D., Glorieux F.H., Pike J.W. Vitamin D. 1997;973-994 Academic Press, New York.
21. Jones G., Strugnell S., DeLuca H.F. Current understanding of the mechanism of action of vitamin D. Physiol Rev. 78:1998;1193-1231.
22. Sasaki H., Harada H., Handa Y., Morino H., Suzawa M., Shimpo E., Katsumata T., Masuhiro Y., Matsuda K., Ebihara K., Ono T., Masushige S., Kato S. Transcriptional activity of a fluorinated vitamin D analog on VDR-RXR mediated gene expression. Biochemistry. 34:1995;370-377.
23. 3 through A-ring modification. Norman A.W., Bouillon R., Thomasset M. Vitamin D. Chemistry, biology and clinical applications of the steroid hormone. 1997;139-146 University of California, Berkeley.
24. Kissmeyer A.M., Binderup E., Binderup L., Mork Hansen C., Andersen N.R., Makin H.L., Schroeder N.J., Shankar V.N., Jones G. Metabolism of the vitamin D analog EB1089 Identification of in vivo and in vitro metabolites and their biological activities . Biochem Pharmacol. 53:1997;1087-1097.
25. 3. Chem Pharm Bull. 44:1996;2280-2286.
26. 3 . Biochem Pharmacol. 41:1991;1601-1606.
27. 3 analogue. Bioorg Med Chem Lett. 2:1992;1713-1716.
28. Masuda S., Strugnell S., Calverley M.J., Makin H.L., Kremer R., Jones G. In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models. J Biol Chem. 269:1994;4794-4803.
29. Langan-Fahey S.M., Tormey D.C., Jordan V.C. Tamoxifen metabolites in patients on long-term adjuvant therapy for breast cancer. Eur J Cancer. 26:1990;883-888.
30. Osborne C.K., Jarman M., McCague R., Coronado E.B., Hilsenbeck S.G., Wakeling A.E. The importance of tamoxifen metabolism in tamoxifen-stimulated breast tumor growth. Cancer Chemother Pharmacol. 34:1994;89-95.
31. Dodge J.A., Lugar C.W., Cho S., Short L.L., Sato M., Yang N.N., Spangle L.A., Martin M.J., Phillips D.L., Glasebrook A.L., Osborne J.J., Frolik C.A., Bryant H.U. Evaluation of the major metabolites of raloxifene as modulators of tissue selectivity. J Steroid Biochem Mol Biol. 61:1997;97-106.