| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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A839977 (A-839977) is a novel and potent P2X7R antagonist with antihyperalgesic and anti-inflammatory activity. The pro-inflammatory cytokine interleukin-1beta (IL-1beta) has been implicated in both inflammatory processes and nociceptive neurotransmission. Activation of P2X7 receptors is the mechanism by which ATP stimulates the rapid maturation and release of IL-1beta from macrophages and microglial cells. Recently, selective P2X7 receptor antagonists have been shown to reduce inflammatory and neuropathic pain in animal models.
| ln Vitro |
A 839977 specifically prevents agonist-induced YO-PRO uptake and IL-1beta release in differentiated human THP-1 cells by inhibiting BzATP-induced calcium influx at the mammalian P2X7 receptor (IC50=20-150 nM). In animal studies, it has been demonstrated to lessen neuropathic pain and inflammation [1]. In optic astrocytes, 839977 (50 nM, 1 hour pretreatment) effectively inhibits the rise in IL-1β initiation that is produced by stress [2].
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| ln Vivo |
In rats, A839977 (30 μmol/kg, 100 μmol/kg, 300 μmol/kg; 30 min preinjection) lowers thermal hyperalgesia in a dose-dependent manner when complete Freund's adjuvant (CFA) is injected plantarly [1]. The CFA model of inflammatory pain in wild-type mice was significantly affected by A839977 (10 μmol/kg, 30 μmol/kg, and 100 μmol/kg; pre-injection for 30 minutes), whereas IL-1alphabeta knockout mice were not significantly affected. Rats are ineffective [1]. In animals with cancer, A839977 reduces the responses of dorsal horn neurons [3].
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| Cell Assay |
RT-PCR[2]
Cell Types: Optic astrocytes Tested Concentrations: 50 nM Incubation Duration: 1 hour (pre-treatment) Experimental Results: Prevents IL-1β initiation in astrocytes |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)), balb/c (Bagg ALBino) mouse and IL-1 (−/−) mice, for CFA-induced chronic inflammation Doses: 30 μmol/kg, 100 μmol/kg, 300 μmol/kg (rat); 10 μmol/kg, 30 μmol/kg, 100 μmol/kg (mouse)
Route of Administration: injection; 30-minute pre-injection Experimental Results: Attenuated CFA-induced thermal hyperalgesia in a dose-related manner in rats and mice, However, it had no effect on IL-1 (−/−) mice. |
| References |
[1]. Honore P, et al. The antihyperalgesic activity of a selective P2X7 receptor antagonist, A-839977, is lost in IL-1alphabeta knockout mice. Behav Brain Res. 2009 Dec 1;204(1):77-81.
[2]. Albalawi F et.al, The P2X7 Receptor Primes IL-1β and the NLRP3 Inflammasome in Astrocytes Exposed to Mechanical Strain. Front Cell Neurosci. 2017 Aug 8;11:227 [3]. Falk S et al.P2X7 receptor-mediated analgesia in cancer-induced bone pain. Neuroscience. 2015 Apr 16; 291:93-105. |
| Molecular Formula |
C19H14CL2N6O
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| Molecular Weight |
413.262
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| Exact Mass |
412.0606
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| CAS # |
870061-27-1
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| SMILES |
ClC1=C(Cl)C(N2N=NN=C2NCC3=CC=CC=C3OC4=NC=CC=C4)=CC=C1
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| Chemical Name |
1-(2,3-dichlorophenyl)-N-{[2-(pyridin-2-yloxy)phenyl]methyl}-1H-1,2,3,4-tetrazol-5-amine
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| Synonyms |
A839977A-839977A 839977
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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 (~241.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.05 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 (6.05 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension 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 (6.05 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 | 2.4198 mL | 12.0989 mL | 24.1978 mL | |
| 5 mM | 0.4840 mL | 2.4198 mL | 4.8396 mL | |
| 10 mM | 0.2420 mL | 1.2099 mL | 2.4198 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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