| 名称 | A-803467 |
| 描述 | A-803467 is a selective NaV1.8 channel blocker. |
| 激酶实验 | Maize HD2, HD1-B, and HD1-A Enzyme Inhibition.: The enzyme liberats tritiated acetic acid from the substrate, which is quantified by scintillation counting. IC50 values are results of triple determinations. A 50 μL sample of maize enzyme (at 30 °C) is incubated (30 min) with 10 μL of total [3H]acetate-prelabeled chicken reticulocyte histones (2 mg/mL). Reaction is stopped by addition of 50 μL of 1 M HCl/0.4 M acetate and 800 μL of ethyl acetate. After centrifugation (1×104 g, 5 min), an aliquot of 600 μL of the upper phase is counted for radioactivity in 3 mL of liquid scintillation cocktail. MC1568 is tested at a starting concentration of 40 μM, and active substances are diluted further. NaB, VPA, TSA, SAHA, 85 TPX, HC-toxin, and tubacin are used as the reference compounds, and blank solvents are used as negative controls. |
| 体外活性 | A-803467剂量依赖性地降低了包括脊神经结扎（ED50 = 47 mg/kg,ip）,坐骨神经损伤（ED50 = 85 mg/kg,ip）,辣椒素 - 诱导的继发性机械性异常性疼痛（ED 50≈100 mg/ kg,腹腔注射）和足底内完全弗氏佐剂注射后的热痛觉过敏（ED 50 = 41 mg/kg,腹腔注射）.与体外对神经元动作电位的影响一致,将A-803467（20 mg/kg,iv）全身给予脊神经结扎的大鼠,明显降低自发的和von Frey hair诱发的脊髓背角宽动态范围神经元,分别降低66%和53%.A-803467对福尔马林诱导的伤害和急性热和术后疼痛,以及化疗引起的疼痛模型（长春新碱）无效. |
| 体内活性 | A-803467以浓度依赖性方式阻断大鼠背根神经节神经元中的河豚毒素 - 抗性（TTX-R）电流,IC50为140 nM,与美西律和拉莫三嗪（IC50> 30 μM）相比更有效。A-803467对于hNaV1.8显示比hNaV1.2,hNaV1.3,hNaV1.5和hNaV1.7通道高300倍至1,000倍的选择性,其IC50分别为7.38 μM,2.45 μM,7.34 μM和6.74 μM。A-803467显示对外周感觉神经元（包括TRPV1,P2X2/3,CaV2.2和KCNQ2/3通道）中表达的其他通道和受体没有显著活性,IC50> 10 μM。A-803467有效阻断重组人类或大鼠Nav1.8 通道,IC50分别为8 nM和45 nM,保持-40 mV电位。在静息状态下,A-803467也有效阻断人NaV1.8通道,IC50为79 nM。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : 8.9 mg/mL (24.87 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.59 mM), Sonication is recommended.
DMSO : 65 mg/mL (181.67 mM), Sonication is recommended.
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| 关键字 | tetrodotoxin-resistant | SodiumChannel | Sodium Channel | sodium | selective | potent | neuropathic | Nav1.8 | Na+ channels | Na(V1.8) channel | Na channels | Inhibitor | inhibit | inflammatory | channel | anti-nociception | A-803467 |
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