7BO6

VDR complex with LCA derivative

7BO6 の概要

• エントリーDOI: 10.2210/pdb7bo6/pdb
• 分子名称: 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)
• 機能のキーワード: nuclear receptor, agonist, transcription
• 由来する生物種: Danio rerio (Zebrafish); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36269.42

構造登録者

Rochel, N. (登録日: 2021-01-24, 公開日: 2021-08-11, 最終更新日: 2024-01-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.86 Å)