| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Gamma-secretase modulator 2 targets gamma-secretase, a multi-subunit protease complex responsible for the cleavage of amyloid precursor protein (APP). Unlike full gamma-secretase inhibitors, this modulator selectively reduces the production of the highly amyloidogenic Abeta(1-42) peptide without completely blocking gamma-secretase activity, thereby preserving essential Notch signaling and other physiological functions.
|
|---|---|
| ln Vitro |
In vitro, gamma-secretase modulator 2 selectively attenuates the production of Abeta(1-42) in cell-based assays. The compound modulates gamma-secretase activity by altering the cleavage site preference of the enzyme, shifting the production profile away from the pathogenic Abeta(1-42) species toward shorter, less amyloidogenic Abeta peptides.
|
| ln Vivo |
In vivo, gamma-secretase modulator 2 has been evaluated in animal models of Alzheimer's disease. Oral administration of the compound reduces brain Abeta(1-42) levels in transgenic mouse models expressing human APP. The selective modulation of gamma-secretase activity leads to a favorable shift in the Abeta peptide profile without the adverse effects associated with complete gamma-secretase inhibition, such as gastrointestinal toxicity and impaired Notch signaling.
|
| Enzyme Assay |
In vitro enzyme assays for gamma-secretase modulator 2 utilize membrane preparations containing gamma-secretase complex, typically derived from cell lines overexpressing APP or from brain tissue. The compound is incubated with the enzyme preparation and APP substrate, and the resulting Abeta peptide products (Abeta(1-40) and Abeta(1-42)) are quantified by ELISA or mass spectrometry. Selectivity is assessed by comparing changes in Abeta(1-42) versus Abeta(1-40) levels.
|
| Cell Assay |
Cellular assays for gamma-secretase modulator 2 are performed using cell lines (e.g., CHO or HEK293 cells) stably expressing APP or APP-derived substrates. Cells are treated with the compound at concentrations ranging from 0.1 nM to 10 uM for 16-24 hours. Abeta(1-40) and Abeta(1-42) levels in the conditioned media are measured by specific ELISA kits. Cytotoxicity is assessed using cell viability assays to ensure compound safety.
|
| Animal Protocol |
In vivo studies for gamma-secretase modulator 2 are conducted in APP transgenic mouse models of Alzheimer's disease. The compound is administered orally at doses of 1-30 mg/kg once or twice daily. After treatment, brain and cerebrospinal fluid (CSF) are collected for Abeta peptide analysis by ELISA or mass spectrometry. Pharmacodynamic biomarkers, including changes in Abeta(1-42) levels, are measured to assess target engagement and efficacy.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of gamma-secretase modulator 2 include good oral bioavailability and brain penetration, which are essential for targeting CNS disorders. The compound is designed to achieve sufficient exposure in the brain to modulate gamma-secretase activity. Metabolic stability and half-life are favorable for once-daily dosing. The compound is typically formulated for oral administration in preclinical studies.
|
| Toxicity/Toxicokinetics |
Toxicological data for gamma-secretase modulator 2 indicate a favorable safety profile compared to full gamma-secretase inhibitors. At therapeutic doses, it does not cause the gastrointestinal toxicity or immunosuppression associated with complete inhibition of gamma-secretase and Notch signaling. Standard preclinical toxicology studies assess effects on body weight, organ function, and histopathology.
|
| Additional Infomation |
Gamma-secretase modulator 2 is a research-use compound not approved for clinical therapeutic applications. It represents a therapeutic strategy for Alzheimer's disease by selectively reducing Abeta(1-42) production without the side effects of full gamma-secretase inhibitors. The compound is used in neuroscience research to study amyloid pathology and the development of disease-modifying therapies.
|
| Molecular Formula |
C25H22N6O2F4
|
|---|---|
| Molecular Weight |
514.47478
|
| Exact Mass |
514.174
|
| CAS # |
1093978-89-2
|
| PubChem CID |
59472574
|
| Appearance |
White to off-white solid powder
|
| Density |
1.43 g/cm3
|
| Boiling Point |
729.8ºC at 760 mmHg
|
| Flash Point |
395.2ºC
|
| LogP |
4.734
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
37
|
| Complexity |
806
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
AAHNBILIYONQLX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H22F4N6O2/c1-15-11-33(14-30-15)21-8-6-16(10-23(21)37-2)19-12-35(32-31-19)22-9-7-17-18(26)4-3-5-20(17)34(24(22)36)13-25(27,28)29/h3-6,8,10-12,14,22H,7,9,13H2,1-2H3
|
| Chemical Name |
6-fluoro-3-[4-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]triazol-1-yl]-1-(2,2,2-trifluoroethyl)-4,5-dihydro-3H-1-benzazepin-2-one
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~194.37 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.86 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 (4.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9437 mL | 9.7187 mL | 19.4375 mL | |
| 5 mM | 0.3887 mL | 1.9437 mL | 3.8875 mL | |
| 10 mM | 0.1944 mL | 0.9719 mL | 1.9437 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
