9rap
VDR complex with UG-635
Structural highlights
FunctionVDRA_DANRE Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Plays a central role in calcium homeostasis.[1] Publication Abstract from PubMedWe report the synthesis and pharmacological evaluation of UG-635, a novel 25-nitro vitamin D analogue bearing a 20-epimeric configuration. Cytotoxicity studies in SH-SY5Y neuroblastoma and HepG2 hepatocarcinoma cells showed that UG-635 is well tolerated at low concentrations but reduces viability at higher doses. Importantly, UG-635 demonstrated protective effects against oxidative stress in neuronal cells and exhibited anti-proliferative activity in breast cancer (MCF7) and osteoblast (MC3T3-E1) models, with efficacy comparable to calcitriol. Structural and crystallographic analyses revealed efficient binding to the vitamin D receptor (VDR), stabilizing its active conformation through favorable interactions with anchoring histidines. These findings highlight UG-635 as a promising vitamin D analogue with potential pharmacological relevance in cancer and neurodegenerative disease contexts, combining anti-proliferative and cytoprotective properties. 25-nitro-20-epi-vitamin D analogue with anti-proliferative and cytoprotective properties: Biological and pharmacological evaluation.,Gomez-Bouzo U, Peluso-Iltis C, Barreiro S, Fernandes C, Verlinden L, Verstuyf A, Borges F, Rochel N, Gomez G, Fall Y Exp Mol Pathol. 2026 Mar;145:105036. doi: 10.1016/j.yexmp.2026.105036. Epub 2026 , Feb 23. PMID:41734645[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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