4LXA

Crystal Structure of Human Beta Secretase in Complex with Compound 11a

4LXA の概要

• エントリーDOI: 10.2210/pdb4lxa/pdb
• 関連するPDBエントリー: 4LXK 4LXM
• 分子名称: Beta-secretase 1, (1R,3S,4S,5R)-3-{4-amino-3-fluoro-5-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]benzyl}-5-[(3-tert-butylbenzyl)amino]tetrahydro-2H-thiopyran-4-ol 1-oxide, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: structure-based drug design, aspartyl protease, membrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 136272.84

構造登録者

Rondeau, J.M.,Bourgier, E. (登録日: 2013-07-29, 公開日: 2013-08-28, 最終更新日: 2024-10-16)

主引用文献

Rueeger, H.,Lueoend, R.,Machauer, R.,Veenstra, S.J.,Jacobson, L.H.,Staufenbiel, M.,Desrayaud, S.,Rondeau, J.M.,Mobitz, H.,Neumann, U.
Discovery of cyclic sulfoxide hydroxyethylamines as potent and selective beta-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid beta-peptides.
Bioorg.Med.Chem.Lett., 23:5300-5306, 2013

PubMed Abstract: Previous structure based optimization in our laboratories led to the identification of a novel, high-affinity cyclic sulfone hydroxyethylamine-derived inhibitor such as 1 that lowers CNS-derived Aβ following oral administration to transgenic APP51/16 mice. Herein we report SAR development in the S3 and S2' subsites of BACE1 for cyclic sulfoxide hydroxyethyl amine inhibitors, the synthetic approaches employed in this effort, and in vivo data for optimized compound such as 11d.

PubMed: 23981898
DOI: 10.1016/j.bmcl.2013.07.071

実験手法

X-RAY DIFFRACTION (1.95 Å)