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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Vitamin D Receptor Agonists: Opportunities and Challenges in Drug Discovery

Author(s): Tadakatsu Takahashi and Kazumi Morikawa

Volume 6, Issue 12, 2006

Page: [1303 - 1316] Pages: 14

DOI: 10.2174/156802606777864917

Price: $65

Abstract

1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an important hormone that regulates metabolism of calcium and phosphorus in small intestine, kidney, and bone, and its physiological action is expressed as ligand-dependent transcription activity mediated by vitamin D receptor (VDR). The VDR is found in various organs and cells including small intestine, kidney, and bone. In addition to the regulation of calcium metabolism, 1,25(OH)2D3 is involved in various biological reactions such as differentiation induction, antiproliferative effect, immunomodulatory effect, and regulation of cytokine and parathyroid hormone secretion. Thus, 1,25(OH)2D3 is expected to become a therapeutic drug for various related diseases. At present, a number of vitamin D derivatives are clinically applied to psoriasis, secondary hyperparathyroidism and osteoporosis but hypercalcemia and hypercalciuria are major concerns. Therefore, the current focus is directed toward new vitamin D derivatives with weak calcemic effects and a wide therapeutic window. In this summary, recent developments of new vitamin D derivatives for application in clinical treatment are described.

Keywords: Vitamin D, vitamin D receptor (VDR), nuclear receptor

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