Simufilam dihydrochloride (PTI-125 dihydrochloride) is a low toxicity, orally active filamin A (FLNA) activator, which can be used for the research of Alzheimer's disease. Simufilam dihydrochloride preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its α7nAChR/TLR4 associations and downstream pathologies.

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

Simufilam dihydrochloride (22 mg/kg; p.o.) robustly reduces FLNAea7nAChR/TLR4 associations. Simufilam dihydrochloride significantly improves spatial memory.