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SEW84 is a potent and selective inhibitor of the Aha1-stimulated Hsp90 ATPase activity without inhibition of basal Hsp90 ATPase. It binds to the C-terminal domain of Aha1 and weakens the Hsp90-Aha1 interaction. SEW84 inhibits Aha1-dependent Hsp90 chaperoning activities including refolding of denatured firefly luciferase (in vitro) and in vivo transcriptional activity of the glucocorticoid receptor and AR androgen receptor in prostate cancer cell-based models. SEW84 preferentially clears Alzheimer disease related phosphorylated aggregation-prone Tau in primary rat cortical neurons.

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