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A-804598 (A 804598) is a structurally novel, CNS penetrant, potent, competitive, and selective antagonist of the purinergic P2X7 receptors (IC50 = 10 nM, 9 nM and 11 nM for rat, mouse and human P2X7 receptors respectively) with potential anti-inflammatory activity. Purinergic P2X7 receptors (P2X7Rs) play an important role in the generation of inflammatory responses during a number of CNS pathologies. A804598 treatment reversed the changes in microglia and astrocytes, reduced/abolished increases in mRNA levels of number of inflammatory markers, including IL-1β, iNOS, CXCR2, and components of inflammatory signaling pathways, such as TLR2, CASP1, NF-kB1 and CREB1, as well in the protein levels of pro-IL-1β and Nf-kB1.
ln Vitro |
In a concentration-dependent manner, pre-incubation with A-804598 (0.1-10 μM; 1 hour) greatly reduces BzATP-induced cell loss. The highest protective effect against BzATP-induced cytotoxicity is shown by 3 μM A-804598[2].
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ln Vivo |
In the lumbar spinal cord in the end stage of the disease, chroni therapy with A-804598 (intraperitoneal injection; 30 mg/kg; five times a week) reduces the expression of LC3B-II and SQSTM1/p62[3].
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Cell Assay |
Cell Cytotoxicity Assay[2]
Cell Types: microglial cell Tested Concentrations: 0.1, 0.3, 1, 3, 10 μM Incubation Duration: 1 hour Experimental Results: Protected against BzATP-induced cytotoxicity in both inactivated and activated microglia. |
Animal Protocol |
Animal/Disease Models: Adult B6 .Cg-Tg (SOD1-G93A) 1Gur/J female mice [3]
Doses: 30 mg/kg Route of Administration: intraperitoneal (ip)injection; five times a week Experimental Results: diminished SQSTM1/p62 expression. |
References |
[1]. Donnelly-Roberts DL et al. [3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology, 2009 Jan, 56(1):223-9.
[2]. Yingbo He et al. The role of microglial P2X7: modulation of cell death and cytokine release. Neuroinflammation, 2017 Jul, 14(1):135. [3]. Paola Fabbrizio et al. P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia.Cell Neurosci, 2017 Aug, 11:249. |
Molecular Formula |
C19H17N5
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Molecular Weight |
315.38
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CAS # |
1125758-85-1
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Related CAS # |
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SMILES |
C[ C@H](/N=C(NC1=C2C=CC=NC2=CC=C1)/NC#N)C3=CC=CC=C3
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Chemical Name |
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.93 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 (7.93 mM) 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; with ultrasonication. 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 (7.93 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 | 3.1708 mL | 15.8539 mL | 31.7078 mL | |
5 mM | 0.6342 mL | 3.1708 mL | 6.3416 mL | |
10 mM | 0.3171 mL | 1.5854 mL | 3.1708 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.
P2X7 activation modulates microtubule-associated protein 1 light chain 3 (LC3)-II in superoxide dismutase 1 (SOD1)-G93A microglia.Front Cell Neurosci.2017 Aug 21;11:249. th> |
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P2X7 induces autophagic flux in SOD1-G93A microglia.Front Cell Neurosci.2017 Aug 21;11:249. td> |
In vivochronic treatment with P2X7 antagonist A-804598 decreases SQSTM1/p62 expression in lumbar spinal cord of SOD1-G93A mice.Front Cell Neurosci.2017 Aug 21;11:249. td> |