4I0D

Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors

4I0D の概要

• エントリーDOI: 10.2210/pdb4i0d/pdb
• 関連するPDBエントリー: 4HZT 4I0E 4I0F 4I0G 4I0Z 4I10 4I12 4I1C
• 分子名称: Beta-secretase 1, ZINC ION, N-(6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-3-(4-propylthiophen-3-yl)-L-alanine, ... (4 entities in total)
• 機能のキーワード: bace, aspartic protease, hydrolysis, 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: 1
• 化学式量合計: 46046.30

構造登録者

Yao, N.,Brecht, E. (登録日: 2012-11-16, 公開日: 2013-10-09, 最終更新日: 2024-11-06)

主引用文献

Xu, Y.Z.,Yuan, S.,Bowers, S.,Hom, R.K.,Chan, W.,Sham, H.L.,Zhu, Y.L.,Beroza, P.,Pan, H.,Brecht, E.,Yao, N.,Lougheed, J.,Yan, J.,Tam, D.,Ren, Z.,Ruslim, L.,Bova, M.P.,Artis, D.R.
Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors.
Bioorg.Med.Chem.Lett., 23:3075-3080, 2013

PubMed Abstract: Utilizing a structure based design approach, combined with extensive medicinal chemistry execution, highly selective, potent and novel BACE1 inhibitor 8 (BACE1 Alpha assay IC50=8nM) was made from a weak μM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed.

PubMed: 23570791
DOI: 10.1016/j.bmcl.2013.03.009

実験手法

X-RAY DIFFRACTION (1.91 Å)