A-740003 |
Catalog No.GC11842
One-Click Copy Product Info
|
A-740003 is an orally active P2X7 receptor antagonist (IC50=40nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 861393-28-4
Sample solution is provided at 25 µL, 10mM.
A-740003 is an orally active P2X7 receptor antagonist (IC50=40nM). A-740003 reduces IL-1β release and pore formation in the cell membrane by inhibiting ATP binding to the P2X7 receptor, while also alleviating neuropathic pain and inflammatory responses by blocking P2X7 receptor activation. A-740003 can be used in research related to neuropathic pain, inflammatory pain, and neuroblastoma[1-4].
In vitro, MC3T3-E1 cells were co-treated with A-740003 (10μM), Wnt3a (20ng/ml), and BzATP (300μM) for 24 hours. A-740003 significantly inhibited the BzATP-induced potentiation of Wnt3a signaling[5]. MC3T3-E1 or UMR-106 cells were incubated with A-740003 (10μM), and proton efflux was measured immediately. A-740003 had no significant effect on basal proton efflux but significantly blocked the sustained phase of the BzATP-induced response in both cell types[6].
In vivo, A-740003 (10μM; 0.5μl/hour) was intracerebroventricularly infused into rats with pilocarpine-induced status epilepticus (SE) for 2 weeks. A-740003 increased the number of Fluoro-Jade B (FJB)-positive neurons in the CA3 region of the hippocampus[7]. A-740003 (100nmol; 0.3μl; single) was injected intracerebroventricularly (into the vlPAG) in a rat model of bone cancer pain. A-740003 antagonized the analgesic effect of tramadol[8].
References:
[1] Janssen B, Vugts DJ, Funke U, et al. Synthesis and initial preclinical evaluation of the P2X7 receptor antagonist [¹¹C]A-740003 as a novel tracer of neuroinflammation. J Labelled Comp Radiopharm. 2014 Jun 30;57(8):509-16.
[2] Honore P, Donnelly-Roberts D, Namovic MT, 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.
[3] Zhang B, Zhang P, Li T, et al. P2X7 Receptor in Microglia Contributes to Propofol-induced Unconsciousness by Regulating Synaptic Plasticity in Mice. Neuroscience. 2023 Jul 15;523:157-172.
[4] Liu Y, Liu Q, Xu Z, et al. P2X7 Receptor acts as a novel target for ameliorating Sepsis-induced skeletal muscle atrophy in mice model. Shock. 2025 Sep 5.
[5] Grol MW, Zelner I, Dixon SJ. P2X₇-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.
[6] Grol MW, Brooks PJ, Pereverzev A, et al. P2X7 nucleotide receptor signaling potentiates the Wnt/β-catenin pathway in cells of the osteoblast lineage. Purinergic Signal. 2016 Sep;12(3):509-20.
[7] Kim JE, Ryu HJ, Kang TC. 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.
[8] Li P, Zhang Q, Xiao Z, et al. Activation of the P2X7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats. Mol Pain. 2018 Jan-Dec;14:1744806918803039.
| Cell experiment [1]: | |
Cell lines | MC3T3-E1 osteoblast-like cells |
Preparation Method | MC3T3-E1 cells were transfected with a β-catenin luciferase reporter, placed in serum-free medium and incubated overnight. The next day, cells were treated with Wnt3a (20ng/ml) or its vehicle and BzATP (300μM) or its vehicle, in the presence or absence of A-740003 (10μM). |
Reaction Conditions | 10μM; 24h |
Applications | A-740003 inhibited BzATP-induced potentiation of Wnt3a signaling in MC3T3-E1 cells. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Rats were intracerebroventricularly infused with A-740003 (10μM; 0.5μl/hour) prior to pilocarpine-induced status epilepticus (SE). Animals were sacrificed for hippocampal analysis. |
Dosage form | 10μM; intracerebroventricular infusion; 0.5μl/hour for 2 weeks |
Applications | A-740003 infusion increased SE-induced neuronal death in the CA3 region, as indicated by increased Fluoro-Jade B positive neurons. |
References: | |
| 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. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1072 mL | 10.5359 mL | 21.0717 mL |
| 5 mM | 421.4 μL | 2.1072 mL | 4.2143 mL |
| 10 mM | 210.7 μL | 1.0536 mL | 2.1072 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)