Vitamin D and Its Synthetic Analogs

Abstract

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.

New Roles for Vitamin D Superagonists: From COVID to Cancer

“…The aim has been to produce analogues with enhanced VDR binding and increased stability to metabolism. The structure of these compounds has been described previously and a further detailed description is beyond the scope of this review ( 34 ). Structural modifications within vitamin D have typically been made in four sites: the side chain, A-ring, CD-ring and triene system.…”

“…Structural modifications within vitamin D have typically been made in four sites: the side chain, A-ring, CD-ring and triene system. More recently non-steroidal vitamin D mimics have also been described ( 34 ). To date, there have been few comparative studies of vitamin D and VDSAs in clinical trials.…”

“…Orientation within the LBP influences agonist activity, and compounds with 20-epi side chain modifications sit inside this pocket to promote coactivator binding, mediating transcription at 100-fold lower concentration than calcitriol ( 40 ). Various additional side chain modifications have also generated ligands with superagonist activity ( 34 ). Removal of C19 from within the A-ring resulted in 19-nor vitamin D compounds (including paricalcitol) with increased pro-differentiation and anti-proliferative activity on cancer cells and decreased calcemic activity.…”

Importancia del metabolismo y consumo de las vitaminas D y C durante la infección por SARS-CoV-2

“…La vitamina D comprende un grupo de prohormonas, la vitamina D2 (ergocalciferol) y la vitamina D3 (colecalciferol) que son precursores principales biológicamente inertes; el colecalciferol se forma a partir de la exposición del 7-dehidrocolesterol en la piel a los rayos UVB; la vitamina D2 se deriva de las plantas y se produce exógenamente por irradiación del ergosterol y entra a la circulación a través de la dieta. En los seres humanos, ambos precursores (D2 y D3) sufren hidroxilación en el hígado para convertirse en 25-hidroxivitamina D [25(OH)D], ésta requiere de una segunda hidroxilación a nivel renal para convertirse 1,25-dihidroxivitamina D [1,25(OH)2D] o calcitriol, el metabolito activo de esta vitamina (23,24).…”

Prospective pilot trial of calcipotriene as a novel topical treatment for acute skin graft versus host disease

“…Calcipotriene is thought to modulate immune responses in the skin by upregulating vitamin D receptors (VDR's) in epidermal nuclei. Calcipotriene has been used in immune-mediated skin dermatoses [3] and for steroid-resistant prurigo nodularis and atopic dermatitis [4].…”