| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Kd: 160 μM (Aβ1-42)[1]. Kd: 337 μM (tau)[1]
The primary targets of Abeta/tau aggregation-IN-1 are the amyloid-beta (Abeta1-42) peptide and the tau protein. The compound binds to these pathological proteins (with KD values of 160 microM for Abeta1-42 and 337 microM for tau) and inhibits the formation of beta-sheets, the secondary structure that drives the aggregation of both Abeta into amyloid plaques and tau into neurofibrillary tangles (NFTs), the two hallmark pathologies of Alzheimer‘s disease. |
|---|---|
| ln Vitro |
The tau aggregation foci are greatly reduced by Aβ/tau aggregation-IN-1 (1 μM; 24 hours; HEK-293 T cells)[1]. Aβ/tau aggregation-IN-1 efficiently inhibits tau aggregation by 71.2%–101.8% and Aβ1–42 aggregation by 84.7%–99.5% when the quinolone ring is N-methylated. Aβ/tau aggregation-IN-1 prevents the production of β-sheets, which in turn prevents self-induced Aβ1-42 aggregation. Aβ/tau aggregation-IN-1 demonstrates specific binding properties with tau and Aβ1-42. Aβ/tau aggregation-IN-1 with Aβ1-42 has a KD value of 160 μM. Aβ/tau aggregation-IN-1 with tau has a KD value of 337 μM. Through noncovalent interactions, tau and Aβ1-42 are interacting with Aβ/tau aggregation-IN-1[1].
In vitro, Abeta/tau aggregation-IN-1 potently inhibits Abeta1-42 beta-sheet formation and tau protein aggregation. When the quinolone ring is N-methylated, the compound inhibits Abeta1-42 aggregation by 84.7%-99.5% and tau aggregation by 71.2%-101.8%. The compound blocks the self-induced aggregation of both proteins by preventing the formation of beta-sheets, thereby interfering with both the nucleation and elongation phases of fibrillogenesis. It has been reported to cross the blood-brain barrier (BBB). |
| ln Vivo |
Specific in vivo activity data for Abeta/tau aggregation-IN-1 is not provided in the available references, though the compound is reported to cross the blood-brain barrier. As a dual inhibitor of both Abeta and tau aggregation, the compound would be expected to reduce both amyloid plaque burden and neurofibrillary tangle formation in transgenic mouse models of Alzheimer's disease (e.g., APP/PS1/Tau triple transgenic mice). In vivo efficacy studies would assess the compound‘s ability to improve cognitive function, reduce protein aggregation, and attenuate neurodegeneration.
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| Enzyme Assay |
The non-cellular activity of Abeta/tau aggregation-IN-1 is assessed using thioflavin T (ThT) fluorescence aggregation assays for both Abeta and tau. For Abeta1-42 aggregation: synthetic Abeta1-42 (25 uM) is incubated with varying concentrations of Abeta/tau aggregation-IN-1 (e.g., 0.1-500 uM) in PBS (pH 7.4) at 37degC for 24-72 hours. ThT fluorescence (excitation 440 nm, emission 485 nm) is measured. For tau aggregation: the tau-derived peptide K18 (containing four microtubule-binding repeats) or full-length tau (2N4R) is incubated with heparin as an inducer in the presence of the compound. Percent inhibition is calculated relative to the vehicle control.
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| Cell Assay |
Immunofluorescence[1]
Cell Types: HEK-293 T cells Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically declined the tau aggregation foci. For cellular assays, neuroblastoma cells (e.g., SH-SY5Y or N2a) expressing tau protein or treated with exogenous tau seeds are used. Cells are treated with Abeta/tau aggregation-IN-1 (1-100 uM) for 24-48 hours. Tau aggregation is assessed by measuring the levels of insoluble tau species using sarkosyl extraction followed by Western blotting with tau-specific antibodies (e.g., AT8 for phosphorylated tau). Alternatively, cells expressing AbetaPP and presenilin mutations are treated with the compound, and secreted Abeta40 and Abeta42 levels are measured by ELISA. |
| Animal Protocol |
No specific in vivo animal protocol for Abeta/tau aggregation-IN-1 is provided. For an in vivo efficacy study, a triple-transgenic mouse model of Alzheimer's disease (e.g., 3xTg-AD mice expressing mutant APP, PSEN1, and MAPT) would be used. Abeta/tau aggregation-IN-1 would be administered intraperitoneally or by oral gavage (e.g., 10-50 mg/kg/day) for 3-6 months. At the end of treatment, mice are sacrificed, and brain tissue is analyzed for Abeta plaque burden (by Thioflavin S or 6E10 immunohistochemistry) and neurofibrillary tangle load (by AT8 or PHF-1 tau immunohistochemistry). Cognitive function is assessed by Morris water maze or contextual fear conditioning.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Abeta/tau aggregation-IN-1 is not provided. The compound is reported to cross the blood-brain barrier (BBB), which is essential for in vivo efficacy in Alzheimer's disease models. As a small molecule (molecular weight approximately 300-400 Da), it is likely to have moderate lipophilicity, which would facilitate passive diffusion across the BBB. Further studies would be needed to characterize its oral bioavailability, half-life, and brain-to-plasma ratio.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided for Abeta/tau aggregation-IN-1. As a research compound for laboratory use, comprehensive toxicology studies are not typically required. The compound should be handled with standard laboratory safety precautions, including the use of appropriate personal protective equipment (PPE) and working in a well-ventilated fume hood. Potential adverse effects at high doses in vivo are not reported.
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| References | |
| Additional Infomation |
Abeta/tau aggregation-IN-1 is a valuable dual-target research tool for Alzheimer‘s disease drug discovery. The compound targets both Abeta and tau aggregation, the two primary protein pathologies in AD, in a single molecule. This dual inhibitory activity makes it unique among anti-amyloid compounds, which typically target only Abeta or only tau. The inhibition of both beta-sheet-forming proteins may offer synergistic therapeutic benefits by addressing both amyloid plaques and neurofibrillary tangles. The compound is characterized by KD values of 160 microM for Abeta1-42 and 337 microM for tau, and it shows high efficacy (84.7%-99.5% inhibition for Abeta and 71.2%-101.8% for tau) when the quinolone ring is N-methylated.
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| Molecular Formula |
C25H21IN2O
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|---|---|
| Molecular Weight |
492.35
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| Exact Mass |
492.069
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| CAS # |
2252162-81-3
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| PubChem CID |
145982772
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
29
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| Complexity |
628
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[N+]1C2=CC=CC=C2C(N)=C2C(/C(=C/C3C4C(C=CC=3)=CC=CC=4)/CCC=12)=O.[I-]
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| InChi Key |
ZPWPPSSEAGEKIT-FLNCGGNMSA-N
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| InChi Code |
InChI=1S/C25H20N2O.HI/c1-27-21-12-5-4-11-20(21)24(26)23-22(27)14-13-18(25(23)28)15-17-9-6-8-16-7-2-3-10-19(16)17;/h2-12,15,26H,13-14H2,1H3;1H/b18-15+;
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| Chemical Name |
(2E)-9-amino-10-methyl-2-(naphthalen-1-ylmethylidene)-3,4-dihydroacridin-10-ium-1-one;iodide
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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 and light. |
| 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: 33.33 mg/mL (67.70 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.03 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.03 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 10.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0311 mL | 10.1554 mL | 20.3108 mL | |
| 5 mM | 0.4062 mL | 2.0311 mL | 4.0622 mL | |
| 10 mM | 0.2031 mL | 1.0155 mL | 2.0311 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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