For many individuals,
in particular during winter, supplementation
with the secosteroid vitamin D
3
is essential for the prevention
of bone disorders, muscle weakness, autoimmune diseases, and possibly
also different types of cancer. Vitamin D
3
acts via its
metabolite 1α,25-dihydroxyvitamin D
3
[
1,25(OH)
2
D
3
]
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)
2
D
3
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.