Journal
CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 6, Issue 12, Pages 1243-1253Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156802606777864908
Keywords
nuclear receptor signaling; vitamin D; vitamin D analogues; vitamin D receptor; coactivator proteins; corepressor proteins
Categories
Ask authors/readers for more resources
The vitamin D receptor (VDR) is an endocrine member of the nuclear receptor superfamily and binds the biologically most active vitamin D metabolite, 1 alpha,25-diliydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3). The VDR ligand-binding domain is a molecular switch, since its ligand-triggered interactions with corepressor and coactivator proteins are the central molecular events of nuclear 1 alpha,25(OH)(2)D-3 signaling. 1 alpha 25(OH)(2)D-3 analogues have been developed with the goal to improve the biological profile of the natural hormone for a therapeutic application either in hyperproliferative diseases, such as psoriasis and different types of cancer, or in bone disorders, such as osteoporosis. Most of the analogues described to date are agonists, with a few having been identified as antagonists. Only the two side chain analogue Gemini and some of its derivatives act under restricted conditions as inverse agonists. In this review we discuss the molecular mechanisms of these different type of analogues based on crystal structure data, molecular dynamics simulations and biochemical assays.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available