|Description||Semagacestat is an inhibitor of the γ-secretase complex that blocks the production of Aβ38 (IC50= 12.0 nM), Aβ40 (IC50= 12.1 nM), and Aβ42 (IC50= 10.9 nM) from H4 human glioma cells stably overexpressing human wild-type APP into the culture medium. In vitro: blocks the production of Aβ38 (IC50= 12.0 nM), Aβ40 (IC50= 12.1 nM), and Aβ42 (IC50= 10.9 nM) without affecting cell viability. In vivo: decreases hippocampal levels of both Aβ42 and Aβ40 at 10 mg/kg (22-23% reduction) and 30 mg/kg (36-41% reduction) and increases β-CTF at 0.3-10 mg/kg in a dose dependent manner with no inhibition on the processing of other γ-secretase substrates, such as Notch, N-cadherin or EphA4, in the brain, but impairs normal cognition in wild-type mice and 3-month-old Tg2576 mice failing to restore cognitive deficits in the Y-maze test.|
|Brife Description||A potent inhibitor of γ-secretase; Blocks Notch signaling (IC50 = 14.1 nM)|
|Appearance||White to off-white solid|
|Synonyms||(2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide; LY 411,575; LY 411575; LY 450139; LY-411,575; LY-411575; LY411,575; LY411575; LY450139; N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; N2-(2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-(5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)alaninamide; Semagacestat; 425386-60-3|
|Solubility||Soluble to 70mg/mL in DMSO, to 41mg/mL in Ethanol|
|Storage||Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -45℃ for long term (months to years).|
|Boiling Point||681.904℃ at 760 mmHg|
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