2QMG

Structure of BACE Bound to SCH745966

2QMG の概要

• エントリーDOI: 10.2210/pdb2qmg/pdb
• 関連するPDBエントリー: 2qk5 2qkj 2qmd 2qmf 2qp8
• 分子名称: Beta-secretase 1, N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R,4R)-4-PHENOXYPYRROLIDIN-2-YL]ETHYL}-3-{[(2R)-2-(METHOXYMETHYL)PYRROLIDIN-1-YL]CARBONYL}-5-METHYLBENZAMIDE, D(-)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: bace1, protease, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, transmembrane, zymogen
• 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: 2
• 化学式量合計: 89394.67

構造登録者

Strickland, C.O.,Iserloh, U. (登録日: 2007-07-16, 公開日: 2008-03-18, 最終更新日: 2024-10-30)

主引用文献

Iserloh, U.,Pan, J.,Stamford, A.W.,Kennedy, M.E.,Zhang, Q.,Zhang, L.,Parker, E.M.,McHugh, N.A.,Favreau, L.,Strickland, C.,Voigt, J.
Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.
Bioorg.Med.Chem.Lett., 18:418-422, 2008

PubMed Abstract: Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.

PubMed: 17980584
DOI: 10.1016/j.bmcl.2007.10.053

実験手法

X-RAY DIFFRACTION (1.89 Å)