gamme-Secretase blocker for A-beta42, A-beta40 and A-beta38; also inhibits Notch signaling
Form:
Free base
Research Area:
Neurological disease
REVIEW Semagacestat (LY 450139) is an inhibitor of the gamma-secretase enzyme. This enzyme is pivotal in the generation of beta-amyloid, a neurotoxic endogenous peptide formed by proteolysis of amyloid precursor protein (APP). Research on laboratory rats suggest that the soluble form of this peptide is a causative agent in the development of Alzheimer's.
REFERENCES
[1]
Imbimbo, Bruno P.; Peretto, Ilaria. Semagacestat, a γ-secretase inhibitor for the potential treatment of Alzheimer's disease. Current Opinion in Investigational Drugs (BioMed Central). (2009) 10(7): 721-730.
[2]
Panza F, Frisardi V, Imbimbo BP, Capurso C, Logroscino G, Sancarlo D, Seripa D, Vendemiale G, Pilotto A, Solfrizzi V. REVIEW: gamma-Secretase inhibitors for the treatment of Alzheimer's disease: The current state. CNS Neurosci Ther. (2010) Oct;16(5): 272-84.
[3]
Schellekens, Harriet; McNamara, Orla; Dinan, Timothy G.; McCarthy, Justin V.; McGlacken, Gerard P.; Cryan, John F. Semagacestat, a gamma-secretase inhibitor, activates the growth hormone secretagogue (GHS-R1a) receptor. Journal of Pharmacy and Pharmacology. (2013) 65(4): 528-538.
[4]
Koenig, Thomas Mitchell; Audia, James Edmund; Mitchell, David; McDaniel, Stacey Leigh; Buccilli, Lynne Ann; Engel, Gary Lowell; Aikins, James Abraham Preparation of lactam derivative useful for inhibiting beta-amyloid peptide release and/or its synthesis PCT Int. Appl. (2002), WO 2002040451 A2 20020523
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