| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Phenserine targets acetylcholinesterase (AChE). It is a potent, non-competitive inhibitor of AChE. By inhibiting AChE, it increases acetylcholine levels in the brain, which may improve cognitive function. It also targets amyloid precursor protein (APP) processing, reducing the production of amyloid-β (Aβ) peptides, which are implicated in Alzheimer's disease pathology.
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| ln Vitro |
Phenserine (1-25 μM; 48 hours; CHO APP751SW cells): APP levels were reduced by 51.4% in APP-treated CHO APP751SW cells, compared to an 18.6% reduction in cells when treated with 10 μM Phenserine [2]. 2]
Phenserine demonstrates potent AChE inhibition in vitro. It is a non-competitive inhibitor of AChE. In addition to its AChE inhibitory activity, phenserine reduces the production of APP and Aβ in cell-based assays. Its dual mechanism of action makes it a unique compound for Alzheimer's disease research. Its IC50 for AChE inhibition and its effects on APP processing have been characterized. |
| ln Vivo |
When cholinergic function is compromised, phenesine (1-4 mg/kg; intraperitoneal injection; 4 days duration; Fischer-344-loaded construct) therapy enhances learning in spatial memory tests [3].
Phenserine has been investigated in vivo for the treatment of Alzheimer's disease. In animal models, it improves cognitive function and reduces amyloid plaque burden. Its ability to increase acetylcholine levels and reduce Aβ production has been demonstrated in preclinical studies. Clinical trials have been conducted for Alzheimer's disease. |
| Enzyme Assay |
Acetylcholinesterase inhibition assays are performed using recombinant or purified AChE enzyme. The enzyme is incubated with the substrate acetylthiocholine in the presence of varying concentrations of Phenserine. The reaction product (thiocholine) is detected using Ellman's reagent (DTNB), which produces a yellow color measured spectrophotometrically at 412 nm. Inhibition is calculated as a percentage of control activity. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate or triplicate.
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| Cell Assay |
Western Blot Analysis[2]
Cell Types: CHO APP751SW Cell Tested Concentrations: 1 μM, 2.5 μM, 5 μM, 10 μM, 25 μM Incubation Duration: 48 hrs (hours) Experimental Results: Cells treated with 10 μM diminished APP levels by 8.6%, while 25 μM concentration diminished APP levels 51.4%%. Cellular AChE inhibition and APP processing are evaluated in neuronal cell lines (e.g., SH-SY5Y) or primary neuronal cultures. Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with Phenserine at various concentrations. AChE activity in cell lysates is measured using the Ellman's assay. APP and Aβ levels in cell lysates and culture supernatants are measured by ELISA or Western blotting. Cell viability is assessed using MTT or LDH assays. Each experiment includes known AChE inhibitors as positive controls. |
| Animal Protocol |
Animal/Disease Models: 344 male Fischer-scopolamine-induced rats (5 months old) [3]
Doses: 1 mg/kg, 2 mg/kg, 4 mg/kg Route of Administration: intraperitoneal (ip) injection; 4 days Experimental Results: Scopolamine treatment Morris water maze performance improved in rats. In vivo efficacy is evaluated in transgenic mouse models of Alzheimer's disease (e.g., APP/PS1 mice). Phenserine is administered orally or intraperitoneally at doses determined by preclinical studies. Cognitive function is assessed using behavioral tests (Morris water maze, novel object recognition). Brain tissue is collected for Aβ plaque quantification and AChE activity measurement. Sample sizes typically range from 8-12 animals per group. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Rapidly absorbed and eliminated from the body. Biological Half-Life 8 to 10 hours. Phenserine has a molecular weight of 337.42 g/mol and a molecular formula of C20H23N3O2. CAS No.: 101246-66-6. Purity: Typically ≥98%. Storage: Typically at -20°C. For research use only. |
| Toxicity/Toxicokinetics |
Phenserine has been evaluated in clinical trials for Alzheimer's disease. It is generally well-tolerated at therapeutic doses. Common adverse effects may include nausea, vomiting, and diarrhea (cholinergic side effects). It has been investigated as a potential disease-modifying therapy due to its dual mechanism of action (AChE inhibition and Aβ reduction). No regulatory approvals have been reported.
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| References | |
| Additional Infomation |
Phenserine was developed by the US biopharmaceutical company Axonyx, which focuses on the treatment of dementia. Phenserine is a next-generation acetylcholinesterase (AChE) inhibitor used to treat Alzheimer's disease (AD). Unlike currently marketed AChE inhibitors, Phenserine has a dual mechanism of action, including anti-amyloid activity, which may have a disease-improving effect on AD patients. If ongoing clinical trials confirm this, Phenserine could open up a completely new avenue for the treatment of AD. On September 20, 2005, Axonyx announced that Phenserine was ineffective in two early-term terminated Phase 3 clinical trials. Drug Indication For the treatment of Alzheimer's disease (AD). Mechanism of Action Phenserine is a highly selective, reversible acetylcholinesterase inhibitor whose mechanism of action is known to improve memory and cognitive abilities in Alzheimer's patients. Phenserine may rapidly concentrate in the brain, thereby reducing the incidence of drug toxicity and side effects.
Pharmacodynamics Phenylserine is a phenylcarbamate derivative of physostigmine and a reversible acetyl-selective cholinesterase inhibitor. In studies on rats with impaired forebrain cholinergic systems, injection of benzylserine significantly reduced the level of β-amyloid precursor protein (β-APP) secreted in the rat's cerebrospinal fluid. A study on cultured human brain cells found that benzylserine reduces Aβ levels by regulating the translation of β-APP. Phenserine is also known as (-)-Phenserine. It is a synthetic carbamate compound structurally related to physostigmine. It acts as a potent, non-competitive AChE inhibitor and reduces APP and Aβ production. It has been investigated for Alzheimer's disease. Clinical trials have been conducted, but no regulatory approvals have been reported. |
| Molecular Formula |
C20H23N3O2
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|---|---|
| Molecular Weight |
337.41552
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| Exact Mass |
337.179
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| CAS # |
101246-66-6
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| Related CAS # |
Buntanetap;116839-68-0
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| PubChem CID |
192706
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.228g/cm3
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| Boiling Point |
468.7ºC at 760mmHg
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| Flash Point |
237.3ºC
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| Vapour Pressure |
5.85E-09mmHg at 25°C
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| Index of Refraction |
1.633
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| LogP |
3.742
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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-QUCCMNQESA-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+/m1/s1
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| Chemical Name |
[(3aR,8bS)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
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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 : ~200 mg/mL (~592.73 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (14.82 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 50.0 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 mg/mL (14.82 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 50.0 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.
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