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ACS chemical neuroscience molecule spotlight on semagacestat (LY450139).ACS 化学生物学分子聚焦：司美格鲁肽（LY450139）。
ACS Chem Neurosci. 2010 Aug 18;1(8):533-4. doi: 10.1021/cn1000606.
2
Design, synthesis, and structure-activity relationship of novel orally efficacious pyrazole/sulfonamide based dihydroquinoline gamma-secretase inhibitors.新型口服有效的基于吡唑/磺酰胺的二氢喹啉γ-分泌酶抑制剂的设计、合成及构效关系
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Differential effects of gamma-secretase and BACE1 inhibition on brain Abeta levels in vitro and in vivo.γ-分泌酶和β-分泌酶1（BACE1）抑制对体外和体内脑β-淀粉样蛋白（Aβ）水平的不同影响。
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The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.阿尔茨海默病的淀粉样蛋白假说：治疗之路上的进展与问题
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Alzheimer's disease: paired helical filaments and cytomembranes.阿尔茨海默病：双螺旋丝与细胞膜
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ACS 化学生物学神经科学分子聚焦 ELND006：另一种 γ-分泌酶抑制剂在临床中失败。

ACS chemical neuroscience molecule spotlight on ELND006: another γ-secretase inhibitor fails in the clinic.

机构信息

Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Vanderbilt University , Nashville, Tennessee 37232-6600, United States.

出版信息

ACS Chem Neurosci. 2011 Jun 15;2(6):279-80. doi: 10.1021/cn2000469.

DOI:10.1021/cn2000469
PMID:22778871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3369733/
Abstract

ELND006 is a novel γ-secretase inhibitor by Elan Corporation that was in the clinic as a potential treatment for Alzheimer's disease (AD). The clinical trial for ELND006 was halted in October 2010 due to liver side effects that are thought to be unrelated to the mechanism of action. However, this represents another small molecule γ-secretase inhibitor that has failed in clinical trials (semagacestat) (http://newsroom.lilly.com/releasedetail.cfm?releaseid=499794) which raises serious questions regarding this mechanism for the treatment of AD.

摘要

ELND006 是一种新型的γ-分泌酶抑制剂，由爱尔兰艾尔建公司研发，曾作为治疗阿尔茨海默病（AD）的潜在药物在临床上使用。由于推测与作用机制无关的肝脏副作用，ELND006 的临床试验于 2010 年 10 月停止。然而，这代表了另一种在临床试验中失败的小分子 γ-分泌酶抑制剂（西玛卡塞他）（http://newsroom.lilly.com/releasedetail.cfm?releaseid=499794），这引发了人们对该机制治疗 AD 的严重质疑。