Development of BACE1 inhibitors for Alzheimer's disease

被引:97
作者
Guo, Tao [1 ]
Hobbs, Doug W. [1 ]
机构
[1] Pharmacopeia Drug Discovery Inc, Princeton, NJ 08543 USA
关键词
Alzheimer's disease; aspartyl protease; beta-secretase; BACE; inhibitors; drug discovery;
D O I
10.2174/092986706777452489
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The production and accumulation of beta-amyloid peptides (A beta) from the beta-amyloid precursor protein (APP) are believed to play a key role in the onset and progression of AD. BACE1 (beta-site APP cleaving enzyme 1) is the protease responsible for the N-terminal cleavage of APP leading to the production of A beta peptides and the development of BACE1 inhibitors as potential therapeutic agents for AD has generated tremendous interests from both academia and the pharmaceutical industry. A wide variety of BACE1 inhibitors have been reported, several of which have demonstrated highly promising efficacy in animal models of AD. This review focuses on recent disclosures of BACE1 inhibitors in the patent and scientific literature, covering the period from approximately May 2004 to November 2005.
引用
收藏
页码:1811 / 1829
页数:19
相关论文
共 139 条
[31]  
DEMONT EH, 2004, Patent No. 2004094430
[32]  
Demont H. E., 2004, PCT Int. Appl, Patent No. [2004050619, WO 2004050619A1 20040617]
[33]   Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice [J].
Dominguez, D ;
Tournoy, J ;
Hartmann, D ;
Huth, T ;
Cryns, K ;
Deforce, S ;
Serneels, L ;
Camacho, IE ;
Marjaux, E ;
Craessaerts, K ;
Roebroek, AJM ;
Schwake, M ;
D'Hooge, R ;
Bach, P ;
Kalinke, U ;
Moechars, D ;
Alzheimer, C ;
Reiss, K ;
Saftig, P ;
De Strooper, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (35) :30797-30806
[34]   BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein [J].
Farzan, M ;
Schnitzler, CE ;
Vasilieva, N ;
Leung, D ;
Choe, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (17) :9712-9717
[35]  
Fillit Howard, 2005, Am J Geriatr Pharmacother, V3, P39, DOI 10.1016/j.amjopharm.2005.03.005
[36]   Notch signals control the fate of immature progenitor cells in the intestine [J].
Fre, S ;
Huyghe, M ;
Mourikis, P ;
Robine, S ;
Louvard, D ;
Artavanis-Tsakonas, S .
NATURE, 2005, 435 (7044) :964-968
[37]   ALZHEIMER-TYPE NEUROPATHOLOGY IN TRANSGENIC MICE OVEREXPRESSING V717F BETA-AMYLOID PRECURSOR PROTEIN [J].
GAMES, D ;
ADAMS, D ;
ALESSANDRINI, R ;
BARBOUR, R ;
BERTHELETTE, P ;
BLACKWELL, C ;
CARR, T ;
CLEMENS, J ;
DONALDSON, T ;
GILLESPIE, F ;
GUIDO, T ;
HAGOPIAN, S ;
JOHNSONWOOD, K ;
KHAN, K ;
LEE, M ;
LEIBOWITZ, P ;
LIEBERBURG, I ;
LITTLE, S ;
MASLIAH, E ;
MCCONLOGUE, L ;
MONTOYAZAVALA, M ;
MUCKE, L ;
PAGANINI, L ;
PENNIMAN, E ;
POWER, M ;
SCHENK, D ;
SEUBERT, P ;
SNYDER, B ;
SORIANO, F ;
TAN, H ;
VITALE, J ;
WADSWORTH, S ;
WOLOZIN, B ;
ZHAO, J .
NATURE, 1995, 373 (6514) :523-527
[38]   Transport characteristics of peptides and peptidomimetics:: II.: Hydroxyethylamine bioisostere-containing peptidomimetics as substrates for the oligopeptide transporter and P-glycoprotein in the intestinal mucosa [J].
Gao, J ;
Winslow, SL ;
Vander Velde, D ;
Aubé, J ;
Borchardt, RT .
JOURNAL OF PEPTIDE RESEARCH, 2001, 57 (05) :361-373
[39]   Design of potent inhibitors for human brain memapsin 2 (β-secretase) [J].
Ghosh, AK ;
Shin, DW ;
Downs, D ;
Koelsch, G ;
Lin, XL ;
Ermolieff, J ;
Tang, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (14) :3522-3523
[40]   Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (β-secretase) [J].
Ghosh, AK ;
Devasamudram, T ;
Hong, L ;
DeZutter, C ;
Xu, XM ;
Weerasena, V ;
Koelsch, G ;
Bilcer, G ;
Tang, J .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (01) :15-20