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Description

A cell permeable, fluorene compound that destabilizes the aggregation state of beta-amyloid oligomers (AbetaO) by directly targeting AbetaO and inhibiting AbetaO binding to synapses. It displays full MC65 protection at 125 nM, with an EC50 of 80 nM in a neuronal MC65 culture-based assay, and substantially reduces intraneuronal AbetaO in primary neuronal culture at concentrations between 100 nM and 10 µ,M. Furthermore, it is shown to significantly reduce amyloid levels by 50% compared with control in vivo in a 5xFAD mice cerebral Abeta amyloidosis model when dosed intracerebroventricularly without apparent toxicity.