Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 ACS chemical neuroscience molecule spotlight on ELND006: another γ-secretase inhibitor fails in the clinic.

Literature DB >> 22778871

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

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.

Entities: Chemical Disease

Keywords: Alzheimer’s disease; ELND006; clinical trials; semagacestat; γ-secretase

Mesh：

Substances：

Year: 2011 PMID： 22778871 PMCID： PMC3369733 DOI： 10.1021/cn2000469

Source DB: PubMed Journal: ACS Chem Neurosci ISSN： 1948-7193 Impact factor: 4.418

6 in total

1. ACS chemical neuroscience molecule spotlight on semagacestat (LY450139).

Authors: Corey R Hopkins
Journal: ACS Chem Neurosci Date: 2010-08-18 Impact factor: 4.418

2. Design, synthesis, and structure-activity relationship of novel orally efficacious pyrazole/sulfonamide based dihydroquinoline gamma-secretase inhibitors.

Authors: Anh P Truong; Danielle L Aubele; Gary D Probst; Martin L Neitzel; Chris M Semko; Simeon Bowers; Darren Dressen; Roy K Hom; Andrei W Konradi; Hing L Sham; Albert W Garofalo; Pamela S Keim; Jing Wu; Michael S Dappen; Karina Wong; Erich Goldbach; Kevin P Quinn; John-Michael Sauer; Elizabeth F Brigham; William Wallace; Lan Nguyen; Susanna S Hemphill; Michael P Bova; Frédérique Bard; Ted A Yednock; Guriqbal Basi
Journal: Bioorg Med Chem Lett Date: 2009-07-23 Impact factor: 2.823

3. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function.

Authors: James P Cleary; Dominic M Walsh; Jacki J Hofmeister; Ganesh M Shankar; Michael A Kuskowski; Dennis J Selkoe; Karen H Ashe
Journal: Nat Neurosci Date: 2004-12-19 Impact factor: 24.884

4. Differential effects of gamma-secretase and BACE1 inhibition on brain Abeta levels in vitro and in vivo.

Authors: Anders Brandt Elvang; Christiane Volbracht; Lars Østergaard Pedersen; Klaus Gjervig Jensen; Jens-Jakob Karlsson; Stine Anna Larsen; Arne Mørk; Tine Bryan Stensbøl; Jesper Frank Bastlund
Journal: J Neurochem Date: 2009-06-10 Impact factor: 5.372

5. Alzheimer's disease: paired helical filaments and cytomembranes.

Authors: E G Gray; M Paula-Barbosa; A Roher
Journal: Neuropathol Appl Neurobiol Date: 1987 Mar-Apr Impact factor: 8.090

Review 6. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.

Authors: John Hardy; Dennis J Selkoe
Journal: Science Date: 2002-07-19 Impact factor: 47.728

6 in total

18 in total

1. Neuropathological and biochemical assessments of an Alzheimer's disease patient treated with the γ-secretase inhibitor semagacestat.

Authors: Alex E Roher; Chera L Maarouf; Tyler A Kokjohn; Charisse M Whiteside; Walter M Kalback; Geidy Serrano; Christine Belden; Carolyn Liebsack; Sandra A Jacobson; Marwan N Sabbagh; Thomas G Beach
Journal: Am J Neurodegener Dis Date: 2014-12-05

Review 2. Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal.

Authors: Chandra Sekhar Kuruva; P Hemachandra Reddy
Journal: Drug Discov Today Date: 2016-10-27 Impact factor: 7.851

3. Tau-derived-hexapeptide 306VQIVYK311 aggregation inhibitors: nitrocatechol moiety as a pharmacophore in drug design.

Authors: Tarek Mohamed; Tuan Hoang; Masoud Jelokhani-Niaraki; Praveen P N Rao
Journal: ACS Chem Neurosci Date: 2013-09-19 Impact factor: 4.418

Review 4. Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases.

Authors: Alberto Lleó; Enrica Cavedo; Lucilla Parnetti; Hugo Vanderstichele; Sanna Kaisa Herukka; Niels Andreasen; Roberta Ghidoni; Piotr Lewczuk; Andreas Jeromin; Bengt Winblad; Magda Tsolaki; Barbara Mroczko; Pieter Jelle Visser; Isabel Santana; Per Svenningsson; Kaj Blennow; Dag Aarsland; José Luis Molinuevo; Henrik Zetterberg; Brit Mollenhauer
Journal: Nat Rev Neurol Date: 2014-12-16 Impact factor: 42.937

5. Subjects harboring presenilin familial Alzheimer's disease mutations exhibit diverse white matter biochemistry alterations.

Authors: Alex E Roher; Chera L Maarouf; Michael Malek-Ahmadi; Jeffrey Wilson; Tyler A Kokjohn; Ian D Daugs; Charisse M Whiteside; Walter M Kalback; Mimi P Macias; Sandra A Jacobson; Marwan N Sabbagh; Bernardino Ghetti; Thomas G Beach
Journal: Am J Neurodegener Dis Date: 2013-09-18