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Semagacestat

CAS No. : 425386-60-3

MCE 国际站：Semagacestat

产品活性：Semagacestat 是一种 γ-secretase 抑制剂，抑制 β-amyloid (Aβ42)，Aβ38 和 Aβ40，IC₅₀ 分别为 10.9，12 和 12.1 nM。也抑制 Notch，IC₅₀ 为 14.1 nM。Semagacestat 可用于阿尔茨海默病的相关研究。

研究领域：Neuronal Signaling  |  Stem Cell/Wnt

作用靶点：γ-secretase  |  Amyloid-β  |  Notch

In Vitro: Semagacestat (LY450139) reduces the secretion of Aβ42, Aβ40, and Aβ38 in 96-well-cultured media and increases β-CTF in cell lysates as expected, although this increase is unexpectedly attenuated at high concentrations.
In cortical neurons (CTX), Semagacestat (LY450139) causes a concentration-dependent decrease in Aβ40 secreted into the medium with IC₅₀ value 111 nM for Semagacestat. Semagacestat causes a concentration-dependent decrease in Aβ40 and Aβ42 secreted into the medium with an IC₅₀ value of 126 and 130 nM, respectively.
Semagacestat (3 Μm; for 4 days) exhibits no significant cell toxicity in Huh7 cells.

In Vivo: Semagacestat (LY450139) is found to decrease both Aβ42 and Aβ40 at 10 mg/kg (22-23% reduction;p<0.01) and increase β-CTF at 0.3-10 mg/kg in a dose-dependent manner (15-162% elevation; p<0.01 at 1-10 mg/kg). The γ-secretase inhibitor, Semagacestat (LY450139), a highly potent low molecular weight compound, significantly reduces β-amyloid (Aβ) levels in cell cultures permanently over-expressing APP and in both wildtype and transgenic APP-expressing mice. Three hours following p.o. dosing of 30 mg/kg Semagacestat levels of Aβ40 are reduced by 43% (unpaired t-test, p=0.002) in the brains of wildtype C57BL/6 mice compare with vehicle treated controls. Subcutaneous administration of Semagacestat (30 mg/kg) transiently decreases the amounts of Aβ40 in the dialysate with a maximum reduction in Aβ40 levels of 80% at 3 h post-dosing (p<0.001).

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