| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
Simufilam dihydrochloride targets filamin A (FLNA), a protein that plays a critical role in cytoskeletal organization and cell signaling. The compound preferentially binds altered FLNA and restores its native conformation. This restoration leads to restoration of receptor and synaptic activities and reduces FLNA's α7nAChR/TLR4 associations and downstream pathologies. The compound also targets NMDAR signaling and Arc expression. It inhibits overactive mTOR signaling. By restoring normal FLNA conformation, the compound improves insulin sensitivity, reduces Aβ42-induced neuroinflammation, and reduces tau protein hyperphosphorylation. These effects suggest potential therapeutic applications in Alzheimer's disease and other neurodegenerative conditions.
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| ln Vitro |
In vitro studies have demonstrated that Simufilam dihydrochloride restores NMDAR signaling and Arc expression. The compound inhibits overactive mTOR signaling by restoring the normal conformation of FLNA. It improves insulin sensitivity in cell-based assays. The compound reduces Aβ42-induced neuroinflammation and tau protein hyperphosphorylation. It preferentially binds altered FLNA and restores its native conformation, leading to restoration of receptor and synaptic activities. The compound reduces FLNA's α7nAChR/TLR4 associations and downstream pathologies. These in vitro findings support its potential as a therapeutic agent for Alzheimer's disease and related conditions.
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| ln Vivo |
In vivo studies of Simufilam dihydrochloride have investigated its effects in animal models of Alzheimer's disease and related conditions. The compound's ability to restore NMDAR signaling and reduce neuroinflammation suggests potential cognitive benefits in vivo. Its effects on insulin sensitivity indicate potential metabolic benefits. The compound's ability to reduce Aβ42-induced neuroinflammation and tau protein hyperphosphorylation suggests disease-modifying potential. As a small molecule modulator of FLNA conformation, it offers a novel approach to treating neurodegenerative diseases. Further research is needed to fully characterize its in vivo pharmacokinetic and pharmacodynamic properties and to evaluate its therapeutic potential in clinical trials.
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| Enzyme Assay |
In vitro receptor binding assays for Simufilam dihydrochloride involve testing its binding to altered filamin A (FLNA). Binding affinity is measured using surface plasmon resonance, isothermal titration calorimetry, or immunoprecipitation assays. The compound's ability to restore FLNA native conformation is assessed using biophysical methods such as circular dichroism or fluorescence spectroscopy. NMDAR signaling is measured by monitoring downstream signaling molecules using Western blotting or ELISA. mTOR signaling activity is assessed by measuring phosphorylation of downstream targets such as S6K and 4E-BP1. Tau phosphorylation is measured using phospho-specific antibodies. Neuroinflammation markers such as cytokines and chemokines are quantified by ELISA. All assays are performed with appropriate controls.
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| Cell Assay |
In vitro cell-based assays for Simufilam dihydrochloride involve culturing neuronal cells to evaluate its effects on NMDAR signaling, mTOR signaling, neuroinflammation, and tau phosphorylation. Cells are treated with varying concentrations of the compound for specified durations. NMDAR signaling is assessed by measuring downstream signaling molecules. mTOR activity is measured by phosphorylation of downstream targets. For neuroinflammation studies, cells are treated with Aβ42 to induce inflammation and the compound's ability to reduce inflammatory markers is assessed. Tau hyperphosphorylation is measured using phospho-specific antibodies. Cell viability is assessed using MTT or similar assays. All experiments are performed in triplicate with appropriate controls to ensure statistical reliability.
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| Animal Protocol |
In vivo animal experiments for Simufilam dihydrochloride utilize rodent models of Alzheimer's disease and related conditions. Animals are administered the compound orally or by other routes, and behavioral, biochemical, and histological parameters are assessed. Cognitive function is evaluated using Morris water maze, novel object recognition, or other behavioral tests. Neuroinflammation markers are measured in brain tissue. Tau phosphorylation and NMDAR signaling are assessed by Western blotting or immunohistochemistry. Insulin sensitivity is evaluated using glucose tolerance tests or insulin tolerance tests. Brain Aβ levels and plaque burden are assessed by ELISA or immunohistochemistry. Control groups receiving vehicle alone are included for comparison. All procedures must comply with institutional animal care and use committee guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Simufilam dihydrochloride reflect its nature as a small molecule modulator. It has a molecular weight of 332.27 and the molecular formula C15H23Cl2N3O. The compound is a dihydrochloride salt, which enhances its aqueous solubility. As a small molecule, it can cross the blood-brain barrier, which is essential for its potential applications in Alzheimer's disease. The compound is expected to be absorbed through the gastrointestinal tract and distributed throughout the body including the central nervous system. Complete pharmacokinetic profiling including half-life, clearance, volume of distribution, and bioavailability would require further systematic studies using appropriate analytical methods such as high-performance liquid chromatography-mass spectrometry.
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| Toxicity/Toxicokinetics |
The toxicity profile of Simufilam dihydrochloride has been evaluated in the context of its development as a therapeutic agent for Alzheimer's disease and related conditions. As a small molecule modulator of FLNA, it has a specific mechanism of action that may limit off-target effects. The compound's ability to restore normal FLNA conformation suggests it may have a favorable safety profile. However, as with all pharmaceuticals, comprehensive toxicology studies including acute, subchronic, and chronic toxicity, genotoxicity, and reproductive toxicity would be required for regulatory approval. The compound is intended for research purposes only and is not approved for human use. Proper handling procedures including use of personal protective equipment are recommended.
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| Additional Infomation |
Simufilam dihydrochloride (PTI-125 dihydrochloride; CAS# 2480226-06-8) is also known as 1-benzyl-8-methyl-1,4,8-triazaspiro[4.5]decan-2-one dihydrochloride. It has the molecular formula C15H21N3O·2HCl (C15H23Cl2N3O) and a molecular weight of 332.27. The compound is a small molecule modulator that preferentially binds altered FLNA and restores its native conformation. It restores NMDAR signaling and Arc expression. The compound inhibits overactive mTOR signaling by restoring FLNA conformation, improves insulin sensitivity, and reduces Aβ42-induced neuroinflammation and tau hyperphosphorylation. It reduces FLNA's α7nAChR/TLR4 associations and downstream pathologies. The compound is being investigated for Alzheimer's disease and is intended for research use only.
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| Molecular Formula |
C15H23CL2N3O
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| Molecular Weight |
332.268621683121
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| Exact Mass |
331.121
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| CAS # |
2480226-06-8
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| Related CAS # |
Simufilam hydrochloride;2480226-07-9;Simufilam;1224591-33-6
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| PubChem CID |
155068887
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
330
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCC2(CC1)NCC(=O)N2CC3=CC=CC=C3.Cl.Cl
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| InChi Key |
IZIPGYSLPYPJDQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H21N3O.2ClH/c1-17-9-7-15(8-10-17)16-11-14(19)18(15)12-13-5-3-2-4-6-13;;/h2-6,16H,7-12H2,1H3;2*1H
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| Chemical Name |
4-benzyl-8-methyl-1,4,8-triazaspiro[4.5]decan-3-one;dihydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0096 mL | 15.0480 mL | 30.0960 mL | |
| 5 mM | 0.6019 mL | 3.0096 mL | 6.0192 mL | |
| 10 mM | 0.3010 mL | 1.5048 mL | 3.0096 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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