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| 25mg |
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Purity: ≥98%
A-740003 is a potent and selective P2X7 receptor antagonist. A-740003 has (IC(50) values = 40 nM for human and 18 nM for rat) as measured by agonist-stimulated changes in intracellular calcium concentrations. A-740003 showed weak or no activity (IC(50) > 10 muM) at other P2 receptors and an array of other neurotransmitter and peptide receptors, ion channels, reuptake sites, and enzymes. A-740003 potently blocked agonist-evoked IL-1beta release (IC(50) = 156 nM) and pore formation (IC(50) = 92 nM) in differentiated human THP-1 cells. A-740003 in vivo produces significant antinociception in animal models of neuropathic and inflammatory pain.
| ln Vitro |
Significant boiling occurs in the sustained phase of the BzATP-sensing reaction when A-438079 or A-740003 (10 μM) is added [1]. Dentate granule cells with SE-conducted TNF-α expression are lessened upon infusion of A-740003. Neuronal death in SE sensors is increased by A-740003 infusion [2]. A-740003 and A-438079 showed noticeably higher potency in P2X7 receptor activation in all species when compared to other clamp antagonists. A-740003 and A-438079 show increased activity in storage and in people compared to the Muse P2X7 receptor [3]. In nursing human THP-1 cells, A-740003 potently inhibits agonist-induced IL-1β release (IC50=156 nM) and pore formation (IC50=92 nM) [4].
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| ln Vivo |
Systemic dosages of A-740003 demonstrated dose-dependent anti-injury effects in a tandem junctional nerve ligation paradigm (ED50=19 mg/kg ip). Additionally, sciatic nerve chronic ischemia and two other forms of neuropathic pain were lessened by A-740003. Furthermore, after carrageenan or Freund's adjuvant plantar model, A-740003 successfully and totally eliminated the heat hyperalgesia (ED50=38 - 54 mg/kg ip). A-740003 does not affect exercise performance at analgesic levels and is ineffective in decreasing normal state acute thermal nociceptors [4].
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| References |
[1]. Grol MW, et al. P2X?-mediated calcium influx triggers a sustained, PI3K-dependent increase in metabolic acid production by osteoblast-like cells. Am J Physiol Endocrinol Metab. 2012 Mar 1;302(5):E561-75.
[2]. Kim JE, et al. P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus. J Neuroinflammation. 2011 Jun 2;8:62. [3]. Donnelly-Roberts DL, et al. Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors.Br J Pharmacol. 2009 Aug;157(7):1203-14. Epub 2009 Jun 22. [4]. Honore P, et al. A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat. J Pharmacol Exp Ther. 2006 Dec;319(3):1376-85. Epub 2006 Sep 18. [5]. Y. H. Gao, et al. Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model. Purinergic Signal. 2017 Jun;13(2):215-225 |
| Molecular Formula |
C26H30N6O3
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|---|---|
| Molecular Weight |
474.565
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| Exact Mass |
474.2379
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| CAS # |
861393-28-4
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| Related CAS # |
861393-28-4;
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| SMILES |
N#C/N=C(NC(NC(CC1=CC(OC)=C(C=C1)OC)=O)C(C)(C)C)\NC2=CC=CC3=NC=CC=C23
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| Chemical Name |
N-[1-[[(Cyanoamino)(5-quinolinylamino)methylene]amino]-2,2-dimethylpropyl]-3,4-dimethoxybenzeneacetamide
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| Synonyms |
A-740003 A 740003 A740003.
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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 : ~50 mg/mL (~105.36 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.27 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1072 mL | 10.5359 mL | 21.0717 mL | |
| 5 mM | 0.4214 mL | 2.1072 mL | 4.2143 mL | |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1072 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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