公开(公告)号：US09074238B2

公开(公告)日：2015-07-07

申请号：US13467036

申请日：2012-05-08

Applicant: Chaur-Jong Hu ,  Po-Ting Chen ,  Rita P.-Y. Chen ,  Steven Sheng-Shih Wang

Inventor： Chaur-Jong Hu ,  Po-Ting Chen ,  Rita P.-Y. Chen ,  Steven Sheng-Shih Wang

IPC: A61K31/235 ,  C12Q1/37 ,  C07C49/248 ,  C07C59/84 ,  C07C59/90 ,  C07K7/06 ,  C07C49/255 ,  C07C49/235 ,  C07C225/22 ,  C12Q1/02 ,  G01N33/50 ,  C07C49/223 ,  C07K14/47

CPC classification number: C12Q1/37 ,  A61K31/235 ,  C07C49/223 ,  C07C49/235 ,  C07C49/248 ,  C07C49/255 ,  C07C59/90 ,  C07C225/22 ,  C07K7/06 ,  C07K14/4711 ,  C12Q1/025 ,  G01N33/5058 ,  G01N2333/4709 ,  G01N2500/00 ,  G01N2800/2821

Abstract: A method of enhancing neprilysin activity and/or degrading amyloid-β peptides and/or oligomers in a subject with Alzheimer's disease is disclosed. The method comprises administering to the subject a compound selected from the group consisting of in a therapeutically effective amount to enhance the neprilysin activity and/or degrade the amyloid-β peptides and oligomers in the subject. Methods of improving symptoms and/or retarding progression of Alzheimer's disease and prophylactic treatment and/or treatment of Alzheimer's disease are also disclosed.

Abstract translation: 增强血清蛋白酶活性和/或降解淀粉样蛋白的方法 公开了具有阿尔茨海默病的受试者中的肽和/或寡聚体。 该方法包括向受试者施用选自治疗有效量的化合物，以增强去血清活性和/或降解淀粉样蛋白; 肽和寡聚体。 还公开了改善阿尔茨海默病症状和/或延缓进展和预防性治疗和/或治疗阿尔茨海默病的方法。

公开(公告)号：US20130102498A1

公开(公告)日：2013-04-25

申请号：US13467036

申请日：2012-05-08

Applicant: Rita P.-Y. Chen ,  Steven Sheng-Shih Wang ,  Chaur-Jong Hu ,  Po-Ting CHEN

Inventor： Rita P.-Y. Chen ,  Steven Sheng-Shih Wang ,  Chaur-Jong Hu ,  Po-Ting CHEN

IPC: C12Q1/37 ,  C07C49/255 ,  C12Q1/02 ,  C07C49/248 ,  C07C49/235 ,  C07C225/22 ,  C07K7/06 ,  C07C59/90

CPC classification number: C12Q1/37 ,  A61K31/235 ,  C07C49/223 ,  C07C49/235 ,  C07C49/248 ,  C07C49/255 ,  C07C59/90 ,  C07C225/22 ,  C07K7/06 ,  C07K14/4711 ,  C12Q1/025 ,  G01N33/5058 ,  G01N2333/4709 ,  G01N2500/00 ,  G01N2800/2821

Abstract: Novel substrates for detection of activity of amyloid beta degrading enzyme, such as Neprilysin (NEP) and insulin degrading enzyme (IDE), associated with Alzheimer's disease, are provided. A quenched fluorogenic peptide substrate containing the first seven residues of the Aβpeptide plus a C-terminal Cys residue to detect neprilysin activity with a fluorophore attached to the C-terminal Cys and a quencher linked to the N-terminus of the peptide is disclosed. An assay system sensitive to endopeptidase activity of NEP and IDE, but insensitive to other Aβ-degrading enzymes is disclosed. Active compounds are identified by a cell-based assay system for high-throughput screening.

Abstract translation: 提供了用于检测与阿尔茨海默氏病有关的淀粉样蛋白β降解酶（例如尼泊替宁（NEP）和胰岛素降解酶（IDE））的活性的新型底物。 公开了含有Abetapeptide加上C末端Cys残基的前七个残基的淬灭的荧光肽底物，以检测与附着于C-末端Cys的荧光团和连接于该肽的N末端的猝灭剂的荧光素活性。 公开了对NEP和IDE的内肽酶活性敏感但对其它Aβ降解酶不敏感的测定系统。 通过用于高通量筛选的基于细胞的测定系统鉴定活性化合物。