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LY-411575

CAS No. : 209984-57-6

產品活性：LY-411575 is a potent γ-secretase inhibitor with IC₅₀ of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with IC₅₀ of 0.39 nM.

研究領域：Neuronal Signaling  |  Stem Cell/Wnt  |  Apoptosis

作用靶點：γ-secretase  |  Notch  |  Apoptosis

In Vitro: LY-411,575 blocks Notch activation, and results in apoptosis in primary and immortalized KS cells. LY-411,575 (500 μM) induces G2/M growth arrest SLK cells. LY411575 treatment significantly decreases the amounts of intracellular HCV RNA with IC₅₀ of 0.56?±?0.20?μM and extracellular HCV particles. LY411575 (0-40?nM) alone or in combination with BMS-790052 (0-40?pM) decreases supernatant infectious titers in a dose-dependent manner, and is synergistic regarding production of infectious virus. LY411575 (10?µM) treatment impairs ROS production in HCVcc-infected cells. LY411575 significantly attenuates EMT by inhibiting the Notch signaling activation in vitro.

In Vivo: LY-411,575 (10 mg/kg) decreases brain and plasma Aβ40 and -42 robustly when chronically administered to TgCRND8 mice. LY411,575 reduces cortical Aβ40 in young transgenic CRND8 mice (ED₅₀ appr 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The extent of intestinal goblet cell hyperplasia induced by LY411,575 (10 mg/kg) is similar in young and aged mice. LY411575 inhibits mouse proliferative vitreoretinopathy (PVR) formation in vivo.

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