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| 5mg |
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| Targets |
gamma-Secretase Modulators target the gamma-secretase enzyme complex, which is responsible for the cleavage of amyloid precursor protein (APP). Unlike gamma-secretase inhibitors, which block all gamma-secretase activity, modulators selectively alter the cleavage site to reduce the production of the pathogenic Aβ42 peptide while preserving other gamma-secretase functions.
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| ln Vitro |
In vitro, gamma-Secretase Modulators inhibit Aβ42 production with an IC₅₀ of 11 nM. The compound shows a high Aβ total/Aβ42 ratio of 1170, indicating selectivity for reducing the pathogenic Aβ42 peptide. This activity is assessed using cell-based or cell-free assays that measure the production of Aβ peptides from APP substrates.
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| ln Vivo |
In vivo activity data for gamma-Secretase Modulators are limited in the available literature. As modulators of gamma-secretase activity, they have potential applications in Alzheimer's disease by reducing the production of neurotoxic Aβ42 aggregates. Further in vivo studies in animal models of Alzheimer's disease are needed to evaluate their efficacy and safety.
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| Enzyme Assay |
In vitro enzyme assays for gamma-Secretase Modulators are performed using purified gamma-secretase enzyme complex or membrane preparations containing the enzyme. The enzyme is incubated with APP substrate in the presence of increasing concentrations of the compound. The production of Aβ peptides (Aβ40 and Aβ42) is measured by ELISA or mass spectrometry, and the IC₅₀ for Aβ42 inhibition is calculated.
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| Cell Assay |
In vitro cellular assays for gamma-Secretase Modulators are performed using cells expressing APP. Cells are treated with the compound, and the levels of Aβ40 and Aβ42 secreted into the culture medium are measured by ELISA. The ratio of Aβ total to Aβ42 is calculated to assess the compound's selectivity for reducing the pathogenic Aβ42 peptide.
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| Animal Protocol |
In vivo animal experiments for gamma-Secretase Modulators are typically conducted in transgenic mouse models of Alzheimer's disease. The compound is administered via oral or intraperitoneal routes, and brain levels of Aβ40 and Aβ42 are measured. Cognitive function is assessed using behavioral tests such as the Morris water maze. Efficacy is evaluated by the reduction of Aβ42 levels and improvement in cognitive performance.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of gamma-Secretase Modulators have been characterized in preclinical studies. The compound has a molecular weight of 483.48 and molecular formula C₂₆H₂₄F₃N₃O₃. It is supplied as a research compound with purity ≥98%. Long-term storage should be in a cool, dry place. Further PK details would be available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Toxicological data for gamma-Secretase Modulators are not extensively reported in the available literature. As a research-use compound, its safety profile has not been formally evaluated in comprehensive preclinical toxicology studies. The compound is intended for research purposes only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
gamma-Secretase Modulators are amyloid-β production inhibitors with CAS number 937812-80-1, molecular formula C₂₆H₂₄F₃N₃O₃, and molecular weight 483.48. They selectively inhibit Aβ42 production with an IC₅₀ of 11 nM and an Aβ total/Aβ42 ratio of 1170. They are used in Alzheimer's disease research. This product is for research use only.
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| Molecular Formula |
C26H24N3O3F3
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|---|---|
| Molecular Weight |
483.48226
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| Exact Mass |
483.177
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| CAS # |
937812-80-1
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| PubChem CID |
24781184
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| Appearance |
White to off-white solid powder
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| Density |
1.37g/cm3
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| LogP |
4.69
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
789
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| Defined Atom Stereocenter Count |
2
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ≥ 100 mg/mL (~206.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.17 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 25.0 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: ≥ 2.5 mg/mL (5.17 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0683 mL | 10.3417 mL | 20.6834 mL | |
| 5 mM | 0.4137 mL | 2.0683 mL | 4.1367 mL | |
| 10 mM | 0.2068 mL | 1.0342 mL | 2.0683 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.
Products are for research use only; We do not sell to patients
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