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A-740003

Catalog No.GC11842

A selective P2X7 antagonist

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A-740003 Chemical Structure

Cas No.: 861393-28-4

Size Price Stock Qty
10mM (in 1mL DMSO)
$56.00
In stock
50mg
$53.00
In stock
100mg
$78.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

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Protocol

Animal experiment:

The response to acute thermal stimulation is determined using a commercially available paw thermal stimulator. Rats are placed individually in Plexiglas cubicles mounted on a glass surface maintained at 30°C and allowed a 30-min habituation period. A thermal stimulus, in the form of radiant heat emitted from a focused projection bulb, is then applied to the plantar surface of each hind paw. In each test session, each rat is tested in three sequential trials at approximately 5-min intervals. Paw-withdrawal latencies (PWLs) are calculated as the median of the two shortest latencies. An assay cut off is set at 20.5 s. A-740003 is injected i.p. 30 min before testing for acute thermal pain.

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.

Background

A-740003 is a selective and competitive antagonist of P2X7 receptor with IC50 values of 40 nM and 18 nM in human and rat, respectively [1].

P2X7 receptors are members of ATP-sensitive ionotropic P2X receptor family (P2X1–P2X7). P2X7 receptors can trigger various responses such as activation of caspases, cytokine release, membrane permeabilization, apoptosis and cell proliferation, in immunologically genetic cells [1].

Activated P2X7 receptors rapidly change intracellular calcium concentrations, the release of interleukin-1β (IL-1β), and cytolytic plasma membrane pore formation. In human THP-1 cells with a macrophage phenotype that P2X7 receptors were expressed, IL-1β release and pore formation were resulted from the activation of P2X7 receptors. A-740003 potently inhibited pore formation (measured by Yo-Pro uptake) with an IC50 value of 92 nM and blocked the release of IL-1β with an IC50 value of 156 nM [1].

Homomeric P2X7 receptors were activated by 2´,3´-O-(4-benzoylbenzoyl)-ATP (BzATP) and ATP at high concentrations. This property made homomeric P2X7 receptors different from other P2 receptor superfamily members. In 1321N1 cells stably expressing P2X7 receptors, BzATP changed intracellular calcium concentrations. A-740003 potently inhibited this change with an IC50 value of 18 nM when rat P2X7 receptors were expressed, and an IC50 value of 40 nM when human P2X7 receptors were expressed. A-740003 also inhibited intracellular Yo-Pro uptake with IC50 values of 138 nM and 93 nM, when the Yo-Pro uptake was mediated by rat and human P2X7 receptors, respectively [1].

Reference:
[1].  Prisca Honore, Diana Donnelly-Roberts, Marian T. Namovic, 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. Journal of Pharmacology and Experimental Therapeutics, 2006, 319:1376-1385.

Chemical Properties

Cas No. 861393-28-4 SDF
Chemical Name N-[1-[(E)-[(cyanoamino)-(quinolin-5-ylamino)methylidene]amino]-2,2-dimethylpropyl]-2-(3,4-dimethoxyphenyl)acetamide
Canonical SMILES CC(C)(C)C(NC(=O)CC1=CC(=C(C=C1)OC)OC)N=C(NC#N)NC2=CC=CC3=C2C=CC=N3
Formula C26H30N6O3 M.Wt 474.57
Solubility ≥ 23.7 mg/mL in DMSO, ≥ 2.48 mg/mL in EtOH with ultrasonic and warming Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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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
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