| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
A-64863 primarily targets the retinoic acid-inducible gene I (RIG-I) protein. It specifically interacts with RIG-I, disrupting its polyubiquitination and thereby blocking downstream signal transduction.
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|---|---|
| ln Vitro |
Its core in vitro activity is immunomodulation: it inhibits RIG-I polyubiquitination, blunting IRF-3 activation and type-I interferon (IFN) production. Functionally, this leads to enhanced cellular susceptibility to viruses such as Hepatitis C Virus (HCV) and Influenza Virus. Typical concentrations range from the low mM to μM levels.
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| ln Vivo |
In vivo, A-64863's effects align with its mechanism of action. In plant models, high-dose or localized administration inhibits type-I IFN production, increasing susceptibility to viral infections. Additionally, it has been shown to alleviate aluminum toxicity stress in plants like Arabidopsis thaliana.
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| Enzyme Assay |
Binding is typically validated by Surface Plasmon Resonance (SPR). The general protocol is as follows:
1. Ligand Immobilization: Recombinant RIG-I protein is immobilized on a CM5 sensor chip via amine coupling. 2. Sample Running: Increasing concentrations (e.g., 0-100 μM) of A-64863 are flowed over the chip surface. 3. Data Acquisition & Analysis: Binding signals are recorded, and the dissociation constant (KD) is determined using software. 4. Controls: A scrambled peptide sequence serves as a negative control. |
| Cell Assay |
A standard cellular assay to assess its functional impact is as follows:
1. Cell Culture: Adherent cells like A549 or HT-29 are cultured in media with 10% FBS. 2. Treatment: At ~80% confluence, cells are treated with A-64863 at final concentrations of 5 mM or 10 mM for varying durations (e.g., 8, 16, 24 hours). 3. Endpoint Detection: Cells are lysed for Western Blot to detect changes in RIG-I ubiquitination or downstream signaling proteins like phosphorylated IRF-3. 4. Viral Challenge Model: To validate function, treated cells are exposed to viruses (e.g., HCV), and viral load is quantified by qPCR. |
| Animal Protocol |
Currently, in vivo studies are more prevalent in plant models. A standard protocol in Arabidopsis thaliana is as follows:
1. Model: Use Arabidopsis thaliana seedlings grown in a controlled environment. 2. Administration: Seedlings are cultured in media supplemented with A-64863. For aluminum toxicity studies, AlCl₃ is also added. 3. Assessment: Parameters such as root elongation inhibition and the activity of antioxidant enzymes (e.g., SOD, POD) are measured. 4. Analysis: The compound's ability to mitigate aluminum-induced oxidative damage is evaluated. |
| ADME/Pharmacokinetics |
Comprehensive PK parameters in mammals are not publicly available. A key study revealed that Cyclo(Phe-Pro) is a diffusible small molecule capable of directly crossing biological membranes in a manner that does not require energy nor membrane transport machinery, suggesting potentially good tissue permeability.
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| Toxicity/Toxicokinetics |
Systematic toxicological data is lacking. However, Material Safety Data Sheets (MSDS) indicate:
Ecotoxicity: Generally considered non-hazardous to water, but should not be released into the environment without a permit. Health Hazards: One MSDS classifies the substance as a R41 (risk of serious damage to eyes) and R48 (danger of serious damage to health by prolonged exposure) health hazard. Standard safety precautions for handling active pharmaceutical ingredients are recommended. |
| References | |
| Additional Infomation |
The cyclo(D-Phe-L-Pro) ring is an organic oxygen and organic nitrogen compound. It is functionally associated with α-amino acids. Pyrrolo[1,2-a]pyrazin-1,4-dione, hexahydro-3-(benzyl)- has been reported in antioxidant bacteria of the genus Streptomyces, Streptomyces simonii, and Vibrio anguillarum, and relevant data are available.
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| Molecular Formula |
C14H16N2O2
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|---|---|
| Molecular Weight |
244.29
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| Exact Mass |
244.121
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| CAS # |
14705-60-3
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| Related CAS # |
Cyclo(L-Phe-L-Pro);3705-26-8
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| PubChem CID |
99895
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
509.5±39.0 °C at 760 mmHg
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| Flash Point |
262.0±27.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.614
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| LogP |
-0.56
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
350
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QZBUWPVZSXDWSB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16N2O2/c17-13-12-7-4-8-16(12)14(18)11(15-13)9-10-5-2-1-3-6-10/h1-3,5-6,11-12H,4,7-9H2,(H,15,17)
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| Chemical Name |
Pyrrolo(2,1-f)pyrazine-1,4-dione, 2,3,6,7,8,8a-hexahydro-3-(phenylmethyl)-
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| Synonyms |
A-64863 A64863A 64863
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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, 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 : ~125 mg/mL (~511.69 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.51 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 20.8 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: ≥ 2.08 mg/mL (8.51 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 20.8 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: ≥ 2.08 mg/mL (8.51 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 | 4.0935 mL | 20.4675 mL | 40.9350 mL | |
| 5 mM | 0.8187 mL | 4.0935 mL | 8.1870 mL | |
| 10 mM | 0.4093 mL | 2.0467 mL | 4.0935 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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