7BO6

VDR complex with LCA derivative

Summary for 7BO6

• Entry DOI: 10.2210/pdb7bo6/pdb
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 1, (4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-(2-methyl-2-oxidanyl-propyl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid, ... (4 entities in total)
• Functional Keywords: nuclear receptor, agonist, transcription
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 2
• Total formula weight: 36269.42

Authors

Rochel, N. (deposition date: 2021-01-24, release date: 2021-08-11, Last modification date: 2024-01-31)

Primary citation

Gaikwad, S.,Gonzalez, C.M.,Vilarino, D.,Lasanta, G.,Villaverde, C.,Mourino, A.,Verlinden, L.,Verstuyf, A.,Peluso-Iltis, C.,Rochel, N.,Berkowska, K.,Marcinkowska, E.
Lithocholic acid-based design of noncalcemic vitamin D receptor agonists.
Bioorg.Chem., 111:104878-104878, 2021

PubMed Abstract: The hypercalcemic effects of the hormone 1α,25-dihydroxyvitamin D (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.

PubMed: 33853023
DOI: 10.1016/j.bioorg.2021.104878

Experimental method

X-RAY DIFFRACTION (2.86 Å)