Simufilam dihydrochloride  (Synonyms: PTI-125 dihydrochloride)

Simufilam dihydrochloride (PTI-125 dihydrochloride) is an orally active FLNA modulator. Simufilam dihydrochloride restores NMDAR signaling and Arc expression. Simufilam dihydrochloride inhibits overactive mTOR signaling by restoring the normal conformation of FLNA, improves insulin sensitivity, reduces Aβ₄₂-induced neuroinflammation and tau protein hyperphosphorylation. Simufilam dihydrochloride can be used for research of Alzheimer's disease^[1][2][3].

Simufilam (1 nM; 1 h) dihydrochloride reduces FLNA-α7nAChR/TLR4 associations, dissociates Aβ₄₂-α7nAChR complexes, restores α7nAChR/NMDAR/IR function, and decreases tau phosphorylation in postmortem human AD brain slices^[2].
Simufilam (1 pM-1 nM; 1 h) dihydrochloride dose-dependently reduces FLNA-α7nAChR/TLR4 associations, Aβ₄₂-α7nAChR complexes, tau phosphorylation, and tau nitration, while restoring NMDAR signaling and Arc expression in postmortem human AD hippocampal slices^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Simufilam (10 mg/kg; i.p.; daily; 2 weeks) dihydrochloride reduces FLNA-α7nAChR/TLR4 associations, tau phosphorylation, Aβ₄₂ aggregates, and inflammatory cytokines, while restoring α7nAChR/NMDAR/IR function in ICV Aβ₄₂-infused mice^[2].
Simufilam dihydrochloride (30 mg/kg/d; p.o.; 2 months) reduces FLNA-α7nAChR/TLR4 associations, tau phosphorylation, Aβ₄₂ deposits, and NFTs, improves NMDAR/IR function and synaptic plasticity, and enhances spatial/working memory and nesting behavior in 3xTg AD mice^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

332.27

C₁₅H₂₃Cl₂N₃O

2480226-06-8

O=C1N(CC2=CC=CC=C2)C3(CCN(C)CC3)NC1.[H]Cl.[H]Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Wang HY, et al. Simufilam suppresses overactive mTOR and restores its sensitivity to insulin in Alzheimer's disease patient lymphocytes. Front Aging. 2023 Jun 29;4:1175601.  [Content Brief]

  [2]. Wang HY, et al. Reducing amyloid-related Alzheimer's disease pathogenesis by a small molecule targeting filamin A. J Neurosci. 2012 Jul 18;32(29):9773-84.  [Content Brief]

  [3]. Wang HY, et al. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Neurobiol Aging. 2017 Jul;55:99-114.  [Content Brief]