| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Posiphen (buntanetap) targets the translation of multiple neurotoxic proteins. It selectively binds to an iron-responsive element (IRE) in the 5' untranslated region of mRNA transcripts encoding amyloid precursor protein (APP), tau, alpha-synuclein, and TDP-43, thereby inhibiting their translation under conditions of elevated intracellular iron.
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| ln Vitro |
In vitro, posiphen reduces APP protein levels and amyloid-β production in neuronal cell cultures. It also inhibits the synthesis of tau, alpha-synuclein, and TDP-43. The compound shows neuroprotective effects in various in vitro models of neurodegeneration and reduces protein levels of APP and Aβ in neuronal cultures.
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| ln Vivo |
In vivo, posiphen has shown efficacy in animal models of Alzheimer's disease and Parkinson's disease. It reduces APP, Aβ, tau, and α-synuclein levels in the brains of wild-type and transgenic mice. The compound is orally bioavailable and brain-penetrant, and has demonstrated improvements in cognitive and motor function in preclinical models.
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| Enzyme Assay |
Non-cellular assays for posiphen include in vitro translation assays to measure inhibition of APP mRNA translation. APP mRNA and a reporter construct are incubated with rabbit reticulocyte lysate and varying concentrations of posiphen. Protein production is measured by ELISA or Western blot. Binding to the IRE in the 5' UTR of APP mRNA can be assessed by electrophoretic mobility shift assays.
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| Cell Assay |
In vitro cellular experiments involve treating neuronal cell lines or primary neurons with posiphen. APP, tau, α-synuclein, and TDP-43 protein levels are measured by Western blot. Amyloid-β production is measured by ELISA. Neuroprotection is assessed in models of oxidative stress or excitotoxicity. The compound's effects on protein translation are confirmed by measuring newly synthesized proteins.
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| Animal Protocol |
In vivo animal studies include transgenic mouse models of Alzheimer's disease (e.g., APP/PS1 mice) and Parkinson's disease. Posiphen is administered orally. Cognitive function is assessed by Morris water maze and other behavioral tests. Brain levels of amyloid-β, tau, α-synuclein, and TDP-43 are measured by biochemical assays.
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| ADME/Pharmacokinetics |
Posiphen is orally bioavailable and brain-penetrant. It has favorable pharmacokinetic properties with good oral absorption and distribution to the brain. The compound has a molecular weight of 337.4 g/mol (C₂₀H₂₃N₃O₂). It is soluble in DMSO and should be stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Posiphen has been evaluated in clinical trials and has shown a favorable safety profile. It is well-tolerated at therapeutic doses. The compound also exhibits weak, non-competitive acetylcholinesterase (AChE) inhibition with an IC₅₀ of 45.3 μM, which is >2000-fold higher than its protein translation inhibition activity, minimizing cholinergic side effects.
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| References |
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| Additional Infomation |
Posiphen is being studied in the clinical trial NCT02925650 (Safety, tolerability, pharmacokinetics and pharmacodynamics of Posiphen® in patients with early Alzheimer's disease).
Posiphen (buntanetap, also known as ANVS-401 or (+)-Phenserine) is an orally bioavailable, brain-penetrant small-molecule translational inhibitor of multiple neurotoxic aggregating proteins (APP, tau, α-synuclein, TDP-43). It is currently in Phase 3 clinical trials for Alzheimer's disease (NCT06709014) and Parkinson's disease (NCT05357989). This product is for research purposes only and is not for human therapeutic use. |
| Molecular Formula |
C20H23N3O2
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|---|---|
| Molecular Weight |
337.423
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| Exact Mass |
337.179
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| CAS # |
116839-68-0
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| Related CAS # |
Phenserine;101246-66-6
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| PubChem CID |
11249342
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
3.683
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
507
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@]12CCN([C@H]1N(C3=C2C=C(C=C3)OC(=O)NC4=CC=CC=C4)C)C
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| InChi Key |
PBHFNBQPZCRWQP-AZUAARDMSA-N
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| InChi Code |
InChI=1S/C20H23N3O2/c1-20-11-12-22(2)18(20)23(3)17-10-9-15(13-16(17)20)25-19(24)21-14-7-5-4-6-8-14/h4-10,13,18H,11-12H2,1-3H3,(H,21,24)/t18-,20+/m0/s1
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| Chemical Name |
[(3aS,8bR)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
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| Synonyms |
(+)-O-(Phenylcarbamoyl)eseroline ANVS401 R-phenserine ANVS-401 Posiphen
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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) |
DMSO : ~230 mg/mL (~681.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.75 mg/mL (17.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5.75 mg/mL (17.04 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9637 mL | 14.8183 mL | 29.6367 mL | |
| 5 mM | 0.5927 mL | 2.9637 mL | 5.9273 mL | |
| 10 mM | 0.2964 mL | 1.4818 mL | 2.9637 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02925650
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT04524351
Conditions:Alzheimer Disease|Parkinson DiseaseProducts are for research use only; We do not sell to patients
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