Semagacestat (LY450139) 425386-60-3

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight:

361.44 Semagacestat (LY450139) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM. Phase 3.






Biological Activity


Semagacestat reduces the secretion of Aβ42, Aβ40 and Aβ38 from H4 human
glioma cells stably overexpressing human wild-type APP into the culture
medium, with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, respectively, without
affecting cell viability. Semagacestat also increases β-CTF in cell
lysates with ECmax of 16.0 nM, and the increase can be
unexpectedly attenuated at high concentrations.


Semagacestat inhibits
Notch signaling with IC50 of 14.1 nM, and shows minimal Notch-sparing
selectivity with Notch IC50/Aβ42 IC50 only 1.3. Semagacestat causes a concentration-dependent decrease in Aβ40 secreted
into the medium with IC50 of 111 nM from murine CTX expressing
endogenous murine APP, but murine Aβ42 formation in CTX is roughly
12-fold less than Aβ40 in accordance with data for neurons from wild
type mice.


Oral administration of Semagacestat (1 mg/kg) to 5.5-month old
APP-transgenic Tg2576 mice significantly ameliorates memory deficits on
spatial working memory using the Y-maze task, which disappears after 8
days subchronic dosing.


LY450139 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.

Contact us if you need more details on 425386-60-3. We are ready to answer your questions on packaging, logistics, certification or any Other aspects about Semagacestat 425386-60-3、LY450139 425386-60-3. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Proteases > Gamma-secretase Inhibitor