GNE-0439
目录号 : GC67949GNE-0439 是一种新型 Nav1.7 选择性抑制剂，IC50 为 0.34 uM，抑制 Nav1.5，IC50 为 38.3 μM。GNE-0439 在膜电位测定中抑制突变体 N1742K 通道(IC50=0.37 uM)。GNE-0439 具有羧酸基团，结合在通道孔外，与已知的选择性 VSD4 结合剂不同。
Cas No.:1241902-40-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
IC50: 0.34 uM (Nav1.7)[1]
GNE-0439 is a novel Nav1.7-selective inhibitor with IC50 of 0.34 uM and inhibits Nav1.5 with an IC50 of 38.3 μM. GNE-0439 inhibits mutant N1742K channels (IC50=0.37 uM) in membrane potential assays. GNE-0439 possesses a carboxylic acid group, binds outside of the channel pore, and is unique compared with known selective VSD4 binders[1].
[1]. Chernov-Rogan T, et al. Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors. Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E792-E801.
| Cas No. | 1241902-40-8 | SDF | Download SDF |
| 分子式 | C21H31NO3 | 分子量 | 345.48 |
| 溶解度 | DMSO : 200 mg/mL (578.90 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8945 mL | 14.4726 mL | 28.9452 mL |
| 5 mM | 0.5789 mL | 2.8945 mL | 5.789 mL |
| 10 mM | 0.2895 mL | 1.4473 mL | 2.8945 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Ectopic expression of Nav1.7 in spinal dorsal horn neurons induced by NGF contributes to neuropathic pain in a mouse spinal cord injury model
Front Mol Neurosci 2023 Mar 3;16:1091096.PMID:36937049DOI:PMC10020601
Neuropathic pain (NP) induced by spinal cord injury (SCI) often causes long-term disturbance for patients, but the mechanisms behind remains unclear. Here, our study showed SCI-induced ectopic expression of Nav1.7 in abundant neurons located in deep and superficial laminae layers of the spinal dorsal horn (SDH) and upregulation of Nav1.7 expression in dorsal root ganglion (DRG) neurons in mice. Pharmacologic studies demonstrated that the efficacy of the blood-brain-barrier (BBB) permeable Nav1.7 inhibitor GNE-0439 for attenuation of NP in SCI mice was significantly better than that of the BBB non-permeable Nav1.7 inhibitor PF-05089771. Moreover, more than 20% of Nav1.7-expressing SDH neurons in SCI mice were activated to express FOS when there were no external stimuli, suggesting that the ectopic expression of Nav1.7 made SDH neurons hypersensitive and Nav1.7-expressing SDH neurons participated in central sensitization and in spontaneous pain and/or walking-evoked mechanical pain. Further investigation showed that NGF, a strong activator of Nav1.7 expression, and its downstream JUN were upregulated after SCI in SDH neurons with similar distribution patterns and in DRG neurons too. In conclusion, our findings showed that the upregulation of Nav1.7 was induced by SCI in both SDH and DRG neurons through increased expression of NGF/JUN, and the inhibition of Nav1.7 in both peripheral and spinal neurons alleviated mechanical pain in SCI mice. These data suggest that BBB permeable Nav1.7 blockers might relieve NP in patients with SCI and that blocking the upregulation of Nav1.7 in the early stage of SCI via selective inhibition of the downstream signaling pathways of NGF or Nav1.7-targeted RNA drugs could be a strategy for therapy of SCI-induced NP.