| 名稱(chēng) | A-803467 |
| 描述 | A-803467 is a selective NaV1.8 channel blocker. |
| 激酶實(shí)驗(yàn) | 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. |
| 體外活性 | A-803467劑量依賴(lài)性地降低了包括脊神經(jīng)結(jié)扎（ED50 = 47 mg/kg,ip）,坐骨神經(jīng)損傷（ED50 = 85 mg/kg,ip）,辣椒素 - 誘導(dǎo)的繼發(fā)性機(jī)械性異常性疼痛（ED 50≈100 mg/ kg,腹腔注射）和足底內(nèi)完全弗氏佐劑注射后的熱痛覺(jué)過(guò)敏（ED 50 = 41 mg/kg,腹腔注射）.與體外對(duì)神經(jīng)元?jiǎng)幼麟娢坏挠绊懸恢?將A-803467（20 mg/kg,iv）全身給予脊神經(jīng)結(jié)扎的大鼠,明顯降低自發(fā)的和von Frey hair誘發(fā)的脊髓背角寬動(dòng)態(tài)范圍神經(jīng)元,分別降低66%和53%.A-803467對(duì)福爾馬林誘導(dǎo)的傷害和急性熱和術(shù)后疼痛,以及化療引起的疼痛模型（長(zhǎng)春新堿）無(wú)效. |
| 體內(nèi)活性 | A-803467以濃度依賴(lài)性方式阻斷大鼠背根神經(jīng)節(jié)神經(jīng)元中的河豚毒素 - 抗性（TTX-R）電流,IC50為140 nM,與美西律和拉莫三嗪（IC50> 30 μM）相比更有效。A-803467對(duì)于hNaV1.8顯示比hNaV1.2,hNaV1.3,hNaV1.5和hNaV1.7通道高300倍至1,000倍的選擇性,其IC50分別為7.38 μM,2.45 μM,7.34 μM和6.74 μM。A-803467顯示對(duì)外周感覺(jué)神經(jīng)元（包括TRPV1,P2X2/3,CaV2.2和KCNQ2/3通道）中表達(dá)的其他通道和受體沒(méi)有顯著活性,IC50> 10 μM。A-803467有效阻斷重組人類(lèi)或大鼠Nav1.8 通道,IC50分別為8 nM和45 nM,保持-40 mV電位。在靜息狀態(tài)下,A-803467也有效阻斷人NaV1.8通道,IC50為79 nM。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 8.9 mg/mL (25 mM)
DMSO : 65 mg/mL (181.67 mM)
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| 關(guān)鍵字 | Sodium Channel | inflammatory | Inhibitor | channel | Nav1.8 | Na channels | neuropathic | anti-nociception | selective | potent | Na+ channels | sodium | tetrodotoxin-resistant | A-803467 | inhibit |
| 相關(guān)產(chǎn)品 | Lidocaine hydrochloride | Benzocaine | Valproic Acid | Lidocaine | Mebeverine hydrochloride | Safinamide | Procaine | Amitriptyline hydrochloride | L-Aspartic aicd sodium | Lidocaine Hydrochloride hydrate | Riluzole | Phenytoin sodium |
| 相關(guān)庫(kù) | 神經(jīng)保護(hù)化合物庫(kù) | 抑制劑庫(kù) | 抗癌活性化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 高選擇性抑制劑庫(kù) | 離子通道庫(kù) | 膜蛋白靶向化合物庫(kù) | 疼痛相關(guān)化合物庫(kù) | PPI抑制劑庫(kù) |