A-740003 | CAS:861393-28-4

Chemscene社は、高品質な低分子化合物を提供しているメーカーです。
Chemscene社のA-740003(CAS:861393-28-4)をご紹介します。

※本製品は研究用です。研究用以外には使用できません。

Name:A-740003; 
Cat. No. :CS-0297
CAS No. :861393-28-4
Formula:C26H30N6O3
M. Wt. : 474.55
Solubility:10 mM in DMSO

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. IC50 & 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].

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. Grol MW, et al. 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. 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. 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.