Authors: Yee, Ying K.; Chintalacharuvu, Subba R.; Lu, Jianfen; Nagpal, Sunil

Source: Mini Reviews in Medicinal Chemistry, Volume 5, Number 8, August 2005 , pp. 761-778(18)

Publisher: Bentham Science Publishers

Abstract:

1, 25-dihydroxyvitamin D3 {1,25-(OH)2D3}, the biologically active form of vitamin D, is an important hormone that is critically required for the maintenance of mineral homeostasis and structural integrity of bones. 1,25-(OH)2D3 accomplishes this by facilitating calcium absorption from the gut and by a direct action on osteoblasts, the bone forming cells. Apart form its classical actions on the gut and bone, 1,25- (OH)2D3 and its synthetic analogs also possess potent anti-proliferative, differentiative and immunomodulatory activities. 1,25-(OH)2D3 exerts these effects through vitamin D receptor (VDR), a ligand-dependent transcription factor that belongs to the superfamily of steroid/thyroid hormone/retinoid nuclear receptors. The presence of VDR in various tissues other than gut and bone, along with their ability to exert differentiation, growth inhibitory and anti-inflammatory action, has set the stage for therapeutic exploitation of VDR ligands for the treatment of various inflammatory indications and cancer. However, the use of VDR ligands in clinic is limited by their major dose-related side effect, namely hypercalcemia/hypercalciuria. Efforts are being undertaken to develop vitamin D receptor modulators (VDRMs) that are tissue-selective and/or gene-selective in their action and these ligands may exhibit increased therapeutic indices. This review explores the recent advances in VDR biology, non-secosteroidal VDR ligands and the current and potential clinical applications of VDR ligands in inflammation and cancer.

Keywords: calcitriol; calcium; homeostasis; immunoregulation; tissue-selective estrogen receptor modulator; gene expression; ligand binding domain; coactivators; heterodimerization; creb

Document Type: Review article

Affiliations: 1: Bone and Inflammation Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN-46285, USA.

Publication date: 2005-08-01

More about this publication?

• The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines.
  
  The scope of Mini-Reviews in Medicinal Chemistry will cover all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies.
  
  Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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