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| 25mg |
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| 50mg |
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| Targets |
Aftin-4 targets γ-secretase, activating the enzyme complex to promote the cleavage of amyloid precursor protein (APP) and increase the production of the neurotoxic Aβ42 peptide, which is a key component of amyloid plaques in Alzheimer's disease.
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| ln Vitro |
In N2a cells, primary neurons, and brain lysates, Aftin-4 specifically and effectively raises Aβ1-42 with an EC50 value of about 30 μM [1].
In vitro studies demonstrate that Aftin-4 activates γ-secretase and promotes the production of Aβ42 from APP in cell-based systems; it is structurally related to roscovitine but lacks CDK inhibitory activity, serving as a specific tool for studying Aβ42 generation. |
| ln Vivo |
Aftin-4 raises Aβ1-42 levels in mice and causes a fast onset of long-lasting toxicity that strongly resembles Alzheimer's disease (AD). The animals were killed between three and fourteen days after injecting varying doses of Aftin-4 (3 to 20 nmol/mouse) into the lateral ventricle. Using a mouse ELISA technique, the amount of Aβ1-42 or Aβ1-40 in the dissected hippocampus was determined. In a dose-dependent manner, Aftin-4 raises the content of Aβ1-42 to a maximum of +216% at the highest studied dose [1].
In vivo, Aftin-4 raises Aβ1-42 levels in mice and causes a rapid onset of long-lasting toxicity that strongly resembles Alzheimer's disease pathology; intracerebroventricular injection of Aftin-4 (3 to 20 nmol/mouse) induces Aβ42 accumulation and neurotoxicity within 3-14 days. |
| Enzyme Assay |
The in vitro γ-secretase activity assay involves incubating Aftin-4 with cell membranes containing γ-secretase complex and a fluorogenic APP-based substrate, measuring the cleavage product via fluorescence detection, with EC50 values calculated from concentration-response curves.
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| Cell Assay |
In vitro cell culture studies utilize neuronal cell lines or primary neurons treated with Aftin-4, measuring Aβ42 levels in culture medium by ELISA, assessing cellular toxicity by LDH release or MTT assays, and evaluating changes in APP processing by Western blotting for C-terminal fragments.
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| Animal Protocol |
In vivo animal experiments involve intracerebroventricular injection of Aftin-4 into mice at doses of 3 to 20 nmol per mouse, followed by assessment of Aβ42 levels in brain tissue by ELISA, evaluation of behavioral deficits in cognitive tests (e.g., Morris water maze), and histopathological analysis of amyloid plaque formation and neurodegeneration.
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| ADME/Pharmacokinetics |
Aftin-4 has a molecular weight of 368.48 g/mol and is soluble in DMSO (≥100 mg/mL); it is typically stored as a powder at -20°C (stable for 3 years) or at 4°C (stable for 2 years), with purity ≥95%.
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| Toxicity/Toxicokinetics |
Toxicological data indicate that Aftin-4 induces rapid-onset neurotoxicity in vivo, consistent with Aβ42 accumulation; the compound is a research tool for modeling Alzheimer's disease and is not intended for therapeutic use, with significant toxicity observed at effective doses in animal models.
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| References | |
| Additional Infomation |
Aftin-4 is a research compound used to study Alzheimer's disease pathogenesis by inducing Aβ42 production and amyloid pathology; it serves as a valuable tool for investigating γ-secretase biology, Aβ toxicity, and potential therapeutic interventions for Alzheimer's disease, though it has not been approved for clinical use.
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| Molecular Formula |
C20H28N6O
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|---|---|
| Molecular Weight |
368.4759
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| Exact Mass |
368.232
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| CAS # |
866893-90-5
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| PubChem CID |
5289296
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| Appearance |
White to off-white solid powder
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| LogP |
3.299
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
27
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| Complexity |
444
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC[C@H](CO)NC1=NC2=C(C(=N1)N(C)CC3=CC=CC=C3)N=CN2C(C)C
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| InChi Key |
YPYWONAECUVKHY-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C20H28N6O/c1-5-16(12-27)22-20-23-18(25(4)11-15-9-7-6-8-10-15)17-19(24-20)26(13-21-17)14(2)3/h6-10,13-14,16,27H,5,11-12H2,1-4H3,(H,22,23,24)/t16-/m1/s1
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| Chemical Name |
(2R)-2-[[6-[benzyl(methyl)amino]-9-propan-2-ylpurin-2-yl]amino]butan-1-ol
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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 (~271.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.78 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 (6.78 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 (6.78 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 | 2.7139 mL | 13.5693 mL | 27.1385 mL | |
| 5 mM | 0.5428 mL | 2.7139 mL | 5.4277 mL | |
| 10 mM | 0.2714 mL | 1.3569 mL | 2.7139 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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