化合物A-803467 T2024

Product Introduction
Bioactivity


英文名: A-803467

描述: A-803467 是有效的、选择性的河豚毒素不敏感型Nav1.8 钠通道阻断剂 。它在炎症性疼痛和神经性疼痛模型中有缓解疼痛作用。它通过与 ATP-binding cassette subfamily G member 2 (ABCG2) 转运蛋白的相互作用，增强了传统抗癌物的化疗敏感性。

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

溶解度: Ethanol : 8.9 mg/mL (25 mM)
DMSO : 35.8 mg/mL (100 mM)


关键字: Sodium Channel | inflammatory | Inhibitor | channel | Nav1.8 | Na channels | neuropathic | anti-nociception | selective | potent | Na+ channels | sodium | tetrodotoxin-resistant | A-803467 | inhibit

相关产品: Vernakalant Hydrochloride | 4-Hydroxycinnamamide | μ-TRTX-Hd1a | Zandatrigine | Tocainide hydrochloride | Cyfluthrin | Dyclonine hydrochloride | Levobupivacaine | Phenytoin | GX-674

相关库: Ion Channel Inhibitor Library | Membrane Protein-targeted Compound Library | Inhibitor Library | Anti-Cancer Active Compound Library | Highly Selective Inhibitor Library | PPI Inhibitor Library | Sodium Channel Blocker Library | Target-Focused Phenotypic Screening Library | Anti-Cardiovascular Disease Compound Library | Bioactive Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途