Simufilam (PTI-125) (hydrochloride) is an orally active filamin A (FLNA) activator with low toxicity that can be used in the Alzheimer's disease research. Simufilam (hydrochloride) preferentially binds to altered FLNA and restores its native conformation, restores receptor and synaptic activities, and reduces its a7nAChR/TLR4 associations and downstream pathologies [1].

Simufilam (1 pM~1 nM) (hydrochloride) dose-dependently improves NMDA/glycine-induced Arc expression [1]. Simufilam (1 nM, 1 hour) (hydrochloride) largely restores filamin A to its native conformation and is effective in normalizing receptor activities in AD frontal cortices. Simufilam (hydrochloride) dose-dependently reduces Ab42-induced FLNA coupling to a7nAChR and TLR4 in both Ab42-treated control and AD hippocampus. Simufilam (hydrochloride) reduces Ab42's binding affinity for a7nAChR, thereby prevents Ab42's signaling and further accumulation on a7nAChRs [1].

Simufilam (P.o.; 2 months) (hydrochloride) restores FLNA to its native conformation. Simufilam (22 mg/kg; p.o.) (hydrochloride) robustly reduces FLNAea7nAChR/TLR4 associations. Simufilam (hydrochloride) significantly improves spatial memory. Simufilam (hydrochloride) significantly improves working memory [1].