| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Αβ42[1]
The primary target of Abeta42-IN-2 is the gamma-secretase complex, an intramembrane protease responsible for the cleavage of the Amyloid Precursor Protein (APP). It functions as a gamma-secretase modulator (GSM), shifting APP processing away from the pathogenic Abeta42 production towards shorter, less toxic Abeta fragments. |
|---|---|
| ln Vitro |
Abeta42-IN-2 demonstrates potent activity in cell-free biochemical assays with an IC50 of 6.5 nM for Abeta42. It specifically inhibits the production of the Abeta42 peptide, showcasing high selectivity by reducing the ratio of Abeta42 to total Abeta peptides, making it a highly efficient GSM.
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| ln Vivo |
In vivo data for Abeta42-IN-2 is limited as it is primarily an in vitro tool. However, as a potent GSM, it is expected to reduce brain Abeta42 levels in animal models of Alzheimer‘s disease, potentially improving cognitive function and reducing amyloid plaque pathology. It can be used for the research of Alzheimer's disease.
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| Enzyme Assay |
Cell-free gamma-secretase assays are performed using purified gamma-secretase complex and a recombinant APP-C100 substrate. The compound is incubated with the enzyme and substrate, and the reaction products are analyzed by ELISA specific for Abeta42 or by mass spectrometry to determine the IC50 for Abeta40 and Abeta42 reduction.
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| Cell Assay |
Primary neurons or APP-overexpressing cell lines (e.g., CHO-APP) are seeded in multi-well plates and treated with serial dilutions of Abeta42-IN-2 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 half-maximal inhibitory concentration (IC50).
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| Animal Protocol |
In vivo studies for gamma-secretase modulators are conducted in transgenic mouse models of Alzheimer‘s disease (e.g., Tg2576 or APP/PS1 mice). Animals receive the test compound via oral gavage or intraperitoneal injection. After treatment, brain tissue and cerebrospinal fluid (CSF) are collected to measure Abeta40 and Abeta42 levels by ELISA, with a key efficacy endpoint being the reduction in the Abeta42/Abeta40 ratio.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) profile of Abeta42-IN-2 is currently being characterized. As a gamma-secretase modulator, its PK properties are optimized to achieve adequate brain penetration and sustained target engagement. Key parameters include oral bioavailability, blood-brain barrier permeability, and half-life.
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| Toxicity/Toxicokinetics |
Toxicological and safety profiles have not been formally established for this specific compound. As a gamma-secretase modulator, it is designed to avoid the mechanism-based toxicities associated with full gamma-secretase inhibitors, such as gastrointestinal and goblet cell metaplasia. Safety assessments are an integral part of its further development.
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| References | |
| Additional Infomation |
Abeta42-IN-2 corresponds to compound 36 in patent WO2016070107. It is a valuable tool for studying the gamma-secretase complex and its role in Alzheimer's disease pathology. It is intended for research use only and has not been approved for clinical applications. It is also known as Abeta42 inhibitor-2.
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| Molecular Formula |
C24H25N6O2
|
|---|---|
| Molecular Weight |
429.494304418564
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| Exact Mass |
430.211
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| CAS # |
1914989-80-2
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| PubChem CID |
134391556
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
575
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C)C1=C(C=CC(C2=CC(C)=C(N=N2)N[C](C)C2C=CC(=CC=2)OC)=N1)N1C=NC(C)=C1 |^1:15|
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| InChi Key |
LUJVPGJMVNXPHO-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C24H26N6O2/c1-15-12-21(20-10-11-22(24(27-20)32-5)30-13-16(2)25-14-30)28-29-23(15)26-17(3)18-6-8-19(31-4)9-7-18/h6-14,17H,1-5H3,(H,26,29)/t17-/m0/s1
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| Chemical Name |
6-[6-methoxy-5-(4-methylimidazol-1-yl)pyridin-2-yl]-N-[(1S)-1-(4-methoxyphenyl)ethyl]-4-methylpyridazin-3-amine
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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: 20 mg/mL (46.46 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.65 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 20.0 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 mg/mL (4.65 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 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 mg/mL (4.65 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 | 2.3283 mL | 11.6417 mL | 23.2834 mL | |
| 5 mM | 0.4657 mL | 2.3283 mL | 4.6567 mL | |
| 10 mM | 0.2328 mL | 1.1642 mL | 2.3283 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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