Vitamin D and Its Synthetic Analogs
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Date
2019-03-27
Authors
Miguel A., Maestro
Ferdinand, Molnar
Carsten, Carlberg
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Medicinal Chemistry
Abstract
For many individuals, in particular during winter, supplementation with the secosteroid vitamin D3 is essential for the prevention of bone disorders, muscle weakness, autoimmune diseases, and possibly also different types of cancer. Vitamin D3 acts via its metabolite 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] as potent agonist of the transcription factor vitamin D receptor (VDR). Thus, vitamin D directly affects chromatin structure and gene regulation at thousands of genomic loci, i.e., the epigenome and transcriptome of its target tissues. Modifications of 1,25(OH)2D3 at its side-chain, A-ring, triene system, or C-ring, alone and in combination, as well as nonsteroidal mimics provided numerous potent VDR agonists and some antagonists. The nearly 150 crystal structures of VDR’s ligand-binding domain with various vitamin D compounds allow a detailed molecular understanding of their action. This review discusses the most important vitamin D analogs presented during the past 10 years and molecular insight derived from new structural information on the VDR protein.
Description
Keywords
LIGAND-BINDING DOMAIN, D-RECEPTOR LIGANDS, HORMONE 1-ALPHA, 25-DIHYDROXYVITAMIN D-3, SIDE-CHAIN ANALOGS
Citation
Miguel A. Maestro, Ferdinand Molnár, and Carsten Carlberg Journal of Medicinal Chemistry 2019 62 (15), 6854-6875 DOI: 10.1021/acs.jmedchem.9b00208