5AVL

Crystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 32b

5AVL の概要

• エントリーDOI: 10.2210/pdb5avl/pdb
• 関連するPDBエントリー: 5avi
• 分子名称: Oxysterols receptor LXR-alpha, Nuclear receptor coactivator 1, 2-[4-[4-[[2-[(2-methylpropan-2-yl)oxycarbonyl]-3-oxidanyl-4-(trifluoromethyl)phenyl]methoxy]phenyl]phenyl]ethanoic acid, ... (4 entities in total)
• 機能のキーワード: agonist, complex, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q13133 Q15788
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36175.03

構造登録者

Matsui, Y.,Hanzawa, H.,Tamaki, K. (登録日: 2015-06-17, 公開日: 2015-08-26, 最終更新日: 2023-11-08)

主引用文献

Matsui, Y.,Yamaguchi, T.,Yamazaki, T.,Yoshida, M.,Arai, M.,Terasaka, N.,Honzumi, S.,Wakabayashi, K.,Hayashi, S.,Nakai, D.,Hanzawa, H.,Tamaki, K.
Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists
Bioorg.Med.Chem.Lett., 25:3914-3920, 2015

PubMed Abstract: To obtain potent liver X receptor (LXR) agonists, a structure-activity relationship study was performed on a series of tert-butyl benzoate analogs. As the crystal structure analysis suggested applicable interactions between the LXR ligand-binding domain and the ligands, two key functional groups were introduced. The introduction of the hydroxyl group on the C6-position of the benzoate part enhanced the agonistic activity in a cell-based assay, and the carboxyl group in terminal improved the pharmacokinetic profile in mice, respectively. The obtained compound 32b increased blood ABCA1 mRNA expression without plasma TG elevation in both mice and cynomolgus monkeys.

PubMed: 26238323
DOI: 10.1016/J.BMCL.2015.07.047

実験手法

X-RAY DIFFRACTION (2.8 Å)