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

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

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