ACS chemical neuroscience molecule spotlight on ELND006: another γ-secretase inhibitor fails in the clinic.
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.
Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center,  Vanderbilt University , Nashville, Tennessee 37232-6600, United States.
Corey R
CR
Hopkins
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D006801:Humans; D009488:Neurosciences / Q000639:trends; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012958:Societies, Scientific; D017211:Treatment Failure
D011480:Protease Inhibitors; D011720:Pyrazoles; D011804:Quinolines; C573127:(R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline; D053829:Amyloid Precursor Protein Secretases