CAS 861393-28-4|A-740003
| Common Name | A-740003 | ||
|---|---|---|---|
| CAS Number | 861393-28-4 | Molecular Weight | 474.555 |
| Density | 1.2±0.1 g/cm3 | Boiling Point | / |
| Molecular Formula | C26H30N6O3 | Melting Point | / |
| MSDS | ChineseUSA | Flash Point | / |
| Symbol | GHS06 | Signal Word | Danger |
Names
| Name | N-[1-[(E)-[(cyanoamino)-(quinolin-5-ylamino)methylidene]amino]-2,2-dimethylpropyl]-2-(3,4-dimethoxyphenyl)acetamide |
|---|---|
| Synonym | More Synonyms |
A-740003 BiologicalActivity
| Description | A-740003 is a potent, selective and competitive P2X7 receptor antagonist with IC50 values are 18 and 40 nM for rat and human P2X7 receptors, respectively. |
|---|---|
| Related Catalog | Signaling Pathways >>Membrane Transporter/Ion Channel >>P2X ReceptorResearch Areas >>Neurological Disease |
| Target | IC50: 18 nM (rat P2X7 receptor), 40 nM (human P2X7 receptor) |
| In Vitro | A 438079 or A 740003 (10 μM) significantly blocks the sustained phase of the BzATP-induced response[1]. A-740003 infusion reduces SE-induced TNF-α expression in dentate granule cells. A-740003 infusions increases SE-induced neuronal death[2]. A-740003 and A-438079 show significantly greater potency in blocking P2X7 receptor activation across all species compared with other antagonists. A-740003 and A-438079 show greater activity at rat and human, as compared with mouse P2X7 receptors[3]. A-740003 potently blocks agonist-evoked IL-1β release with (IC50=156 nM) and pore formation (IC50=92 nM) in differentiated human THP-1 cells[4]. |
| In Vivo | Systemic administration of A-740003 produces dose-dependent antinociception in a spinal nerve ligation model (ED50=19 mg/kg i.p.) in the rat. A-740003 also attenuates tactile allodynia in two other models of neuropathic pain, chronic constriction injury of the sciatic nerve and vincristine-induced neuropathy. In addition, A-740003 effectively reduces thermal hyperalgesia observed following intraplantar administration of carrageenan or complete Freund's adjuvant (ED50=38-54 mg/kg i.p.). A-740003 is ineffective in attenuating acute thermal nociception in normal rats and does not alter motor performance at analgesic doses[4]. |
| Animal Admin | 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. |
Chemical & Physical Properties
| Density | 1.2±0.1 g/cm3 |
|---|---|
| Molecular Formula | C26H30N6O3 |
| Molecular Weight | 474.555 |
| Exact Mass | 474.237946 |
| PSA | 120.66000 |
| LogP | 2.77 |
| Index of Refraction | 1.597 |
| InChIKey | PUHSRMSFDASMAE-UHFFFAOYSA-N |
| SMILES | COc1ccc(CC(=O)NC(N=C(NC#N)Nc2cccc3ncccc23)C(C)(C)C)cc1OC |
| Storage condition | 2-8℃ |
Safety Information
| Symbol | GHS06 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H301 |
| Precautionary Statements | P301 + P310 |
| RIDADR | UN 2811 6.1 / PGIII |
Articles1
More Articles| Disruption in connexin-based communication is associated with intracellular Ca²⁺ signal alterations in astrocytes from Niemann-Pick type C mice. PLoS ONE 8 , e71361, (2013) Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evide... |
Synonyms
| N-{1-[N''-Cyano-N'-(quinolin-5-yl)carbamimidamido]-2,2-dimethylpropyl}-2-(3,4-dimethoxyphenyl)acetamide |
| N-(1-{(E)-[(Cyanoamino)(5-quinolinylamino)methylene]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide |
| cc-516 |
| UNII:532OV6WA05 |
| Benzeneacetamide, N-[1-[[(1E)-(cyanoamino)(5-quinolinylamino)methylene]amino]-2,2-dimethylpropyl]-3,4-dimethoxy- |
| CS-0297 |
| A-740003 |
