| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
Plasminogen activator inhibitor-1 (PAI-1) [1]
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| ln Vitro |
Using a reconstituted assay system, Aleplasinin (PAZ-417) dose-dependently eliminated the inhibition of plasmin-mediated Aβ degradation by PAI-1. Specifically, tPA/plasminogen-mediated Aβ degradation was abolished by PAI-1 in vitro, and this inhibition was reversed by PAZ-417 in a dose-dependent manner. [1]
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| ln Vivo |
Treatment with Aleplasinin (PAZ-417) lowered brain Aβ levels and reversed hippocampal long-term potentiation (LTP) and memory deficits in Alzheimer's disease transgenic mice. Additionally, a decrease in plasma Aβ levels was observed following PAZ-417 treatment. Only the brain-penetrating PAI inhibitor PAZ-417 improved memory deficiency, suggesting that central, not peripheral, PAI-1 contributes to AD pathology. [1]
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| Enzyme Assay |
A reconstituted assay system was used to evaluate the effect of Aleplasinin (PAZ-417) on PAI-1 inhibition of plasmin-mediated Aβ degradation. In this system, tPA and plasminogen were incubated with Aβ in the presence of PAI-1. PAI-1 abolished tPA/plasminogen-mediated Aβ degradation. The specific inhibitor PAZ-417 was then added, and it was demonstrated that PAZ-417 dose-dependently eliminated the inhibitory effect of PAI-1, thereby restoring Aβ degradation by the tPA/plasminogen cascade. [1]
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| Animal Protocol |
Alzheimer's disease transgenic mice were used for in vivo efficacy studies. Aleplasinin (PAZ-417) was administered to these mice, and its effects were assessed by measuring brain and plasma Aβ levels, evaluating hippocampal long-term potentiation (LTP), and testing memory performance. The compound was noted to be brain-penetrating. Specific details regarding formulation, dose, route, or frequency of administration were not provided in the reference. [1]
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| References | |
| Additional Infomation |
Aleplasinin is an organic molecular entity. Aleplasinin has been used in research on Alzheimer's disease.
Aleplasinin (PAZ-417) was discovered through a systematic screening for biologically active compounds that regulate PAI-1 activity. The study provides a proof of concept that pharmacological inhibition of PAI-1 can enhance central plasmin activity and Aβ clearance, offering a potential therapeutic strategy for Alzheimer's disease. The authors observed that in AD mouse hippocampus, tPA activities were strikingly declined while PAI-1 levels were markedly elevated. Inhibition of PAI-1 by PAZ-417 partially rescued hippocampal tPA activities. [1] |
| Molecular Formula |
C28H27NO3
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|---|---|
| Molecular Weight |
425.51888
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| Exact Mass |
425.199
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| CAS # |
481629-87-2
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| PubChem CID |
10224267
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.229
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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 |
6
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| Heavy Atom Count |
32
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| Complexity |
675
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(O)C(C1=CN(CC2=CC=C(C(C)(C)C)C=C2)C3=C1C=C(C4=CC=CC(C)=C4)C=C3)=O
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| InChi Key |
HSXLMAFNWCSZGP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H27NO3/c1-18-6-5-7-20(14-18)21-10-13-25-23(15-21)24(26(30)27(31)32)17-29(25)16-19-8-11-22(12-9-19)28(2,3)4/h5-15,17H,16H2,1-4H3,(H,31,32)
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| Chemical Name |
2-[1-[(4-tert-butylphenyl)methyl]-5-(3-methylphenyl)indol-3-yl]-2-oxoacetic acid
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~250 mg/mL (~587.52 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (20.8 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.08 mg/mL (4.89 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 DMSO stock solution (20.8 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.89 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 DMSO stock solution (20.8 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3501 mL | 11.7503 mL | 23.5007 mL | |
| 5 mM | 0.4700 mL | 2.3501 mL | 4.7001 mL | |
| 10 mM | 0.2350 mL | 1.1750 mL | 2.3501 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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