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- W2975979178 abstract "Genetic evidence points to deposition of amyloid-β (Aβ) as a causal factor for Alzheimer's disease. Aβ generation is initiated when β-secretase (BACE1) cleaves the amyloid precursor protein. Starting with an oxazine lead 1, we describe the discovery of a thiazine-based BACE1 inhibitor 5 with robust Aβ reduction in vivo at low concentrations, leading to a low projected human dose of 14 mg/day where 5 achieved sustained Aβ reduction of 80% at trough level." @default.
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- W2975979178 date "2019-09-24" @default.
- W2975979178 modified "2023-09-26" @default.
- W2975979178 title "Discovery of an Extremely Potent Thiazine-Based β-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose" @default.
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- W2975979178 doi "https://doi.org/10.1021/acs.jmedchem.9b01140" @default.
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