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- W4200139356 abstract "Pharmacological activation of the E3 ligase Parkin represents a rational therapeutic intervention for the treatment of Parkinson's disease. Here we identify several compounds that enhance the activity of wildtype Parkin in the presence of phospho-ubiquitin and act as positive allosteric modulators (PAMs). While these compounds activate Parkin in a series of biochemical assays, they do not act by thermally destabilizing Parkin and fail to enhance the Parkin translocation rate to mitochondria or to enact mitophagy in cell-based assays. We conclude that in the context of the cellular milieu the therapeutic window to pharmacologically activate Parkin is very narrow." @default.
- W4200139356 created "2021-12-31" @default.
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- W4200139356 date "2022-01-01" @default.
- W4200139356 modified "2023-10-17" @default.
- W4200139356 title "Discovery of small-molecule positive allosteric modulators of Parkin E3 ligase" @default.
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- W4200139356 doi "https://doi.org/10.1016/j.isci.2021.103650" @default.
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