| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
gamma-secretase[1]
The primary target of gamma-secretase modulator 1 hydrochloride is the gamma-secretase complex, an intramembrane protease involved in the processing of various transmembrane proteins including APP. It acts as a gamma-secretase modulator (GSM), which does not block the enzyme's activity but alters its cleavage site preference. |
|---|---|
| ln Vitro |
In cell-free assays using purified gamma-secretase and recombinant substrate, gamma-secretase modulator 1 hydrochloride reduces the production of the Abeta42 peptide. It effectively shifts APP processing towards the production of shorter, less amyloidogenic Abeta fragments without completely inhibiting the essential functions of the gamma-secretase complex.
|
| ln Vivo |
In vivo data for gamma-secretase modulator 1 hydrochloride is currently limited, as it is primarily used as a research tool in cell-based systems. As a potent GSM, it is expected to lower brain Abeta42 levels and alter the amyloid plaque pathology in animal models of Alzheimer‘s disease, but such studies have not been widely reported.
|
| Enzyme Assay |
Cell-free assays using solubilized gamma-secretase complex and a recombinant APP-C100-flag substrate are performed. The compound is pre-incubated with the enzyme, and the reaction is initiated by adding the substrate. After incubation, Abeta40 and Abeta42 levels are quantified by specific ELISA kits to determine the IC50.
|
| Cell Assay |
Cellular assays are performed in CHO-APP (Chinese hamster ovary cells overexpressing APP) or primary neuronal cultures. Cells are seeded in 96-well plates and treated with a dilution series of gamma-secretase modulator 1 hydrochloride for 16-24 hours. The supernatant is collected and analyzed for Abeta40 and Abeta42 concentrations using a sensitive and specific ELISA.
|
| Animal Protocol |
In vivo studies are conducted in APP-transgenic mouse models (e.g., Tg2576). Mice are administered gamma-secretase modulator 1 hydrochloride via oral gavage or intraperitoneal injection. After treatment, the animals are sacrificed, and brain homogenates and CSF are analyzed for Abeta40 and Abeta42 levels using ELISA to assess the compound‘s efficacy in reducing the pathogenic Abeta42 isoform.
|
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of gamma-secretase modulator 1 hydrochloride are being characterized to support its potential as an in vivo probe. Key parameters being evaluated include oral bioavailability, brain penetration, and metabolic stability, which are crucial for its use in animal models of Alzheimer's disease.
|
| Toxicity/Toxicokinetics |
Toxicological data is limited as this compound is a research tool. Gamma-secretase modulators are generally considered to have a better safety profile than full inhibitors because they preserve the enzyme‘s critical functions, such as Notch signaling, thereby avoiding mechanism-based toxicities like gastrointestinal bleeding.
|
| References | |
| Additional Infomation |
Gamma-secretase modulator 1 hydrochloride has a molecular formula of C24H25ClN4OS and a molecular weight of 453.00. It is supplied as a hydrochloride salt. The compound is used exclusively for laboratory research purposes and is not intended for diagnostic or therapeutic use in humans. It is stored at 4degC, sealed, and away from moisture.
|
| Molecular Formula |
C24H25CLN4OS
|
|---|---|
| Molecular Weight |
452.999502897263
|
| Exact Mass |
452.143
|
| CAS # |
2741571-83-3
|
| Related CAS # |
gamma-secretase modulator 1;1172637-87-4
|
| PubChem CID |
145712306
|
| Appearance |
Off-white to yellow solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
31
|
| Complexity |
559
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(S3)CCCC4C5=CC=CC=C5)OC.Cl
|
| InChi Key |
LKCKOISQTRXFGY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H24N4OS.ClH/c1-16-14-28(15-25-16)20-12-11-18(13-21(20)29-2)26-24-27-23-19(9-6-10-22(23)30-24)17-7-4-3-5-8-17;/h3-5,7-8,11-15,19H,6,9-10H2,1-2H3,(H,26,27);1H
|
| Chemical Name |
N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4-phenyl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine;hydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment, 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)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (220.75 mM)
H2O: < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.52 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 (5.52 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 (5.52 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 | 2.2075 mL | 11.0375 mL | 22.0751 mL | |
| 5 mM | 0.4415 mL | 2.2075 mL | 4.4150 mL | |
| 10 mM | 0.2208 mL | 1.1038 mL | 2.2075 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
