3V66

HUMAN SQUALENE SYNTHASE IN COMPLEX WITH 2-(1-{2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl}-4-piperidinyl)acetic acid

3V66 の概要

• エントリーDOI: 10.2210/pdb3v66/pdb
• 関連するPDBエントリー: 3ASX 3Q2Z 3Q30
• 分子名称: Squalene synthase, PHOSPHATE ION, (1-{[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl}piperidin-4-yl)acetic acid, ... (4 entities in total)
• 機能のキーワード: terpenoid synthase fold, isoprene biosynthesis, lipid synthesis, multifunctional enzyme, oxidoreductase, steroid biosynthesis, sterol biosynthesis, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Multi-pass membrane protein: P37268
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39800.69

構造登録者

Suzuki, M.,Ohtsuka, M.,Ohki, H.,Haginoya, N.,Itoh, M.,Sugita, K.,Usui, H.,Ichikawa, M.,Higashihashi, N. (登録日: 2011-12-18, 公開日: 2012-12-19, 最終更新日: 2023-11-08)

主引用文献

Ichikawa, M.,Ohtsuka, M.,Ohki, H.,Haginoya, N.,Itoh, M.,Sugita, K.,Usui, H.,Suzuki, M.,Terayama, K.,Kanda, A.
Discovery of novel tricyclic compounds as squalene synthase inhibitors
Bioorg.Med.Chem., 20:3072-3093, 2012

PubMed Abstract: In the present article, we have reported the design, synthesis, and identification of highly potent benzhydrol derivatives as squalene synthase inhibitors (compound 1). Unfortunately, the in vivo efficacies of the compounds were not enough for acquiring the clinical candidate. We continued our investigation to obtain a more in vivo efficacious template than the benzhydrol template. In our effort, we focused on a benzoxazepine ring and designed a new tricyclic scaffold by the incorporation of heterocycle into it. Prepared pyrrolobenzoxazepine derivatives showed further efficient in vitro and in vivo activities.

PubMed: 22464687
DOI: 10.1016/j.bmc.2012.02.054

実験手法

X-RAY DIFFRACTION (1.8 Å)