| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
IC50: 0.014 μM (Aβ42, human), 0.017 μM (Aβ42, mouse)[1]
The primary target of gamma-Secretase modulator 4 is the gamma-secretase complex, an intramembrane protease. It functions as a modulator, altering the enzyme‘s cleavage site preference on the Amyloid Precursor Protein (APP) to reduce the formation of the neurotoxic Abeta42 peptide without completely inhibiting the enzyme's other essential functions. |
|---|---|
| ln Vitro |
In cell-free biochemical assays, gamma-Secretase modulator 4 potently reduces Abeta42 levels with an IC50 of 0.014 uM in human samples and 0.017 uM in mouse samples. This demonstrates its high potency and cross-species activity, making it a valuable in vivo tool for studying Alzheimer‘s disease.
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| ln Vivo |
In vivo data for gamma-Secretase modulator 4 is currently inferred from its potent in vitro activity. As a powerful GSM, it is expected to effectively lower Abeta42 levels in the brain and cerebrospinal fluid (CSF) of animal models, potentially modifying amyloid plaque pathology. It is a research tool and not a therapeutic.
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| Enzyme Assay |
Cell-free assays using solubilized gamma-secretase complex and a recombinant APP-C100 substrate are performed. The compound is incubated with the enzyme and substrate, and the reaction products are analyzed by a specific ELISA for Abeta42 or by mass spectrometry to determine the IC50 for the reduction of the Abeta42 peptide.
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| Cell Assay |
Cellular assays are performed in CHO-APP (Chinese hamster ovary cells overexpressing APP) or human neuroglioma H4 cells. Cells are treated with serial dilutions of gamma-Secretase modulator 4 for 18-24 hours. The conditioned media is collected, and the levels of secreted Abeta40 and Abeta42 peptides are quantified using specific sandwich ELISA kits to calculate the IC50.
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| Animal Protocol |
In vivo studies are conducted in transgenic mouse models of Alzheimer's disease (e.g., APP/PS1 mice). Animals receive gamma-Secretase modulator 4 via oral gavage. After treatment, brain tissue and cerebrospinal fluid (CSF) are collected to measure Abeta40 and Abeta42 levels by ELISA. Histological analysis of brain sections is performed to assess changes in amyloid plaque burden.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) profile of gamma-Secretase modulator 4 has been evaluated in mice and humans. It exhibits cross-species activity with IC50 values of 0.017 uM in mice and 0.014 uM in humans, indicating good target engagement at the molecular level. Its PK properties are optimized for CNS penetration.
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| Toxicity/Toxicokinetics |
Toxicological profiles for this specific modulator are not well-documented. As a gamma-secretase modulator, it is designed to avoid the intestinal toxicity associated with full gamma-secretase inhibitors by preserving Notch signaling. The compound is for research use only, and safety is assumed to be manageable at effective doses.
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| References | |
| Additional Infomation |
gamma-Secretase modulator 4 is identified as a potent GSM, with the chemical name N-(3-fluorophenyl)-5-(4-fluorophenoxy)-4-methyl-thiophene-2-carboxamide and a molecular formula of C23H19FN4O2 (MW 402.42). It is a research-grade compound used exclusively for laboratory studies related to Alzheimer‘s disease and is not approved for human use.
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| Molecular Formula |
C23H19FN4O2
|
|---|---|
| Molecular Weight |
402.42
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| Exact Mass |
402.149
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| CAS # |
1420200-82-3
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| PubChem CID |
91844707
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
733.8±60.0 °C at 760 mmHg
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| Flash Point |
397.6±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.680
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| LogP |
5.43
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
|
| Complexity |
671
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=C(C=CC=C1F)[C@H]2C3=NC(=CN3CCO2)C4=CC5=C(N4)C=CC(=C5OC)C#N
|
| InChi Key |
UBJJQXXWGRHIDV-QFIPXVFZSA-N
|
| InChi Code |
InChI=1S/C23H19FN4O2/c1-13-15(4-3-5-17(13)24)22-23-27-20(12-28(23)8-9-30-22)19-10-16-18(26-19)7-6-14(11-25)21(16)29-2/h3-7,10,12,22,26H,8-9H2,1-2H3/t22-/m0/s1
|
| Chemical Name |
2-[(8S)-8-(3-fluoro-2-methylphenyl)-6,8-dihydro-5H-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1H-indole-5-carbonitrile
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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 : ~100 mg/mL (~248.50 mM)
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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 | 2.4850 mL | 12.4248 mL | 24.8497 mL | |
| 5 mM | 0.4970 mL | 2.4850 mL | 4.9699 mL | |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.4850 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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