Structure-based design of potent and selective cell-permeable inhibitors of human β-secretase (BACE-1)

被引：266

作者：

Stachel, SJ

Coburn, CA

Steele, TG

Jones, KG

Loutzenhiser, EF

Gregro, AR

Rajapakse, HA

Lai, MT

Crouthamel, MC

Xu, M

Tugusheva, K

Lineberger, JE

Pietrak, BL

Espeseth, AS

Shi, XP

Chen-Dodson, E

Holloway, MK

Munshi, S

Simon, AJ

Kuo, L

Vacca, JP

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Biol Chem, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Mol Syst, West Point, PA 19486 USA

[4] Merck Res Labs, Dept Biol Struct, West Point, PA 19486 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 26期

关键词：

D O I：

10.1021/jm049379g

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe the development of cell-permeable beta-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell-based assay (IC50 < 100 nM), these inhibitors display impressive selectivity against other biologically relevant aspartyl proteases.

引用

页码：6447 / 6450

页数：4

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