7bo6
From Proteopedia
VDR complex with LCA derivative
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 PubMedThe hypercalcemic effects of the hormone 1alpha,25-dihydroxyvitamin D(3) (calcitriol) and most of known vitamin D metabolites and analogs call for the development of non secosteroidal vitamin D receptor (VDR) ligands as new selective and noncalcemic agonists for treatment of hyperproliferative diseases. We report on the in silico design and stereoselective synthesis of six lithocholic acid derivatives as well as on the calcemic activity of a potent LCA derivative and its crystallographic structure in complex with zVDR LBD. The low calcemic activity of this compound in comparison with the native hormone makes it of potential therapeutic value. Structure-function relationships provide the basis for the development of even more potent and selective lithocholic acid-based VDR ligands. Lithocholic acid-based design of noncalcemic vitamin D receptor agonists.,Gaikwad S, Gonzalez CM, Vilarino D, Lasanta G, Villaverde C, Mourino A, Verlinden L, Verstuyf A, Peluso-Iltis C, Rochel N, Berkowska K, Marcinkowska E Bioorg Chem. 2021 Jun;111:104878. doi: 10.1016/j.bioorg.2021.104878. Epub 2021 , Mar 30. PMID:33853023[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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