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• W2326435909 abstract "The “Notch-sparing” γ-secretase inhibitor (GSI) BMS-708,163 (Avagacestat) is currently in phase II clinical trials for Alzheimer’s disease. Unlike previously failed GSIs, BMS-708,163 is considered to be a promising drug candidate because of its reported Notch-sparing activity for the inhibition of Aβ production over Notch cleavage. We now report that BMS-708,163 binds directly to the presenilin-1 N-terminal fragment and that binding can be challenged by other pan-GSIs, but not by γ-secretase modulators. Furthermore, BMS-708,163 blocks the binding of four different active site-directed GSI photoaffinity probes. We therefore report that this compound acts as a nonselective γ-secretase inhibitor." @default.
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• W2326435909 date "2012-09-04" @default.
• W2326435909 modified "2023-10-16" @default.
• W2326435909 title "BMS-708,163 Targets Presenilin and Lacks Notch-Sparing Activity" @default.
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• W2326435909 doi "https://doi.org/10.1021/bi301137h" @default.
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