3N4L

BACE-1 in complex with ELN380842

3N4L の概要

• エントリーDOI: 10.2210/pdb3n4l/pdb
• 分子名称: Beta-secretase 1, N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(1H-pyrazol-1-yl)phenyl]cyclohexyl}amino)propyl]acetamide (3 entities in total)
• 機能のキーワード: bace, hydroxyethylamine, beta secretase, alzheimer's disease, ad, beta-amyloid precursor protein, beta-app, 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: 137783.06

構造登録者

Yao, N.H. (登録日: 2010-05-21, 公開日: 2010-11-24, 最終更新日: 2024-10-30)

主引用文献

Truong, A.P.,Probst, G.D.,Aquino, J.,Fang, L.,Brogley, L.,Sealy, J.M.,Hom, R.K.,Tucker, J.A.,John, V.,Tung, J.S.,Pleiss, M.A.,Konradi, A.W.,Sham, H.L.,Dappen, M.S.,Toth, G.,Yao, N.,Brecht, E.,Pan, H.,Artis, D.R.,Ruslim, L.,Bova, M.P.,Sinha, S.,Yednock, T.A.,Zmolek, W.,Quinn, K.P.,Sauer, J.M.
Improving the permeability of the hydroxyethylamine BACE-1 inhibitors: structure-activity relationship of P2' substituents.
Bioorg.Med.Chem.Lett., 20:4789-4794, 2010

PubMed Abstract: Herein we describe further evolution of hydroxyethylamine inhibitors of BACE-1 with enhanced permeability characteristics necessary for CNS penetration. Variation at the P2' position of the inhibitor with more polar substituents led to compounds 19 and 32, which retained the potency of more lipophilic analog 1 but with much higher observed passive permeability in MDCK cellular assay.

PubMed: 20634069
DOI: 10.1016/j.bmcl.2010.06.112

実験手法

X-RAY DIFFRACTION (2.7 Å)