4DJX

Structure of BACE Bound to 5-(3-(5-chloropyridin-3-yl)phenyl)-5-cyclopropyl-2-imino-3-methylimidazolidin-4-one

4DJX の概要

• エントリーDOI: 10.2210/pdb4djx/pdb
• 関連するPDBエントリー: 4DJU 4DJV 4DJW 4DJY
• 分子名称: Beta-secretase 1, (2E,5R)-5-[3-(5-chloropyridin-3-yl)phenyl]-5-cyclopropyl-2-imino-3-methylimidazolidin-4-one, L(+)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: bace1, alzheimers, 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: 2
• 化学式量合計: 93481.64

構造登録者

Strickland, C.,Cumming, J. (登録日: 2012-02-02, 公開日: 2012-03-21, 最終更新日: 2012-04-04)

主引用文献

Cumming, J.N.,Smith, E.M.,Wang, L.,Misiaszek, J.,Durkin, J.,Pan, J.,Iserloh, U.,Wu, Y.,Zhu, Z.,Strickland, C.,Voigt, J.,Chen, X.,Kennedy, M.E.,Kuvelkar, R.,Hyde, L.A.,Cox, K.,Favreau, L.,Czarniecki, M.F.,Greenlee, W.J.,McKittrick, B.A.,Parker, E.M.,Stamford, A.W.
Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor.
Bioorg.Med.Chem.Lett., 22:2444-2449, 2012

PubMed Abstract: From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Aβ following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound.

PubMed: 22390835
DOI: 10.1016/j.bmcl.2012.02.013

実験手法

X-RAY DIFFRACTION (1.5 Å)