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- W3091670521 abstract "Inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been extensively pursued as potential disease-modifying treatment for Alzheimer's disease (AD). Clinical failures with BACE inhibitors have progressively raised the bar forever cleaner candidates with reduced cardiovascular liability, toxicity risk, and increased selectivity over cathepsin D (CatD) and BACE2.This review provides an overview of patented BACE1 inhibitors between 2011 and 2020 per pharmaceutical company or research group and highlights the progress that was made in dialing out toxicity liabilities.Despite an increasingly crowded IP situation, significant progress was made using highly complex chemistry in avoiding toxicity liabilities, with BACE1/BACE2 selectivity being the most remarkable achievement. However, clinical trial data suggest on-target toxicity is likely a contributing factor, which implies the only potential future of BACE1 inhibitors lies in careful titration of highly selective compounds in early populations where the amyloid burden is still minimal as prophylactic therapy, or as an affordable oral maintenance therapy following amyloid-clearing therapies." @default.
- W3091670521 created "2020-10-08" @default.
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- W3091670521 date "2020-12-17" @default.
- W3091670521 modified "2023-10-03" @default.
- W3091670521 title "Small-molecule BACE1 inhibitors: a patent literature review (2011 to 2020)" @default.
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- W3091670521 doi "https://doi.org/10.1080/13543776.2021.1832463" @default.
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