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Beta-Amyloid Oligomer Antagonists

Recent work (Krafft et al., Cell 2013) has demonstrated that amyloid beta oligomers are the synaptotoxic entity at the earliest stages of Alzheimer's Disease. Acelot has identified novel brain-penetrant small molecule antagonists of synaptotoxic amyloid oligomer action.

jps_oliginh

Acelot has identified several families of potential oligomer antagonists via the JPS approach. These were tested in a high-quality neuronal assay that evaluates the "health" of neurons. Specifically, the assay measures amyloid-beta oligomer induced decreases in membrane trafficking in mature primary neuronal cultures.

The identified Acelot compounds show potent antagonist activity, some with nanomolar potency. This is a remarkable result, given that the exact mechanism-of-action is still being investigated and only membrane trafficking data were available as input to JPS. In addition, all Acelot compounds show a variety of novel structural scaffolds, opening new opportunities for the development of Alzheimer's Disease cures with minimal side-effects.

All lead candidates are currently being tested in further in-vitro and in-vivo assays.

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(This work is funded in part by the National Science Foundation.)