Dimethyl Fumarate
(Synonyms: 富马酸二甲酯) 目录号 : GC16590
An antioxidant with immunological actions
Cas No.:624-49-7
Sample solution is provided at 25 µL, 10mM.
Dimethyl fumarate is a nuclear factor (erythroid-derived)-like 2 (Nrf2) pathway activator and induces upregulation of antioxidant gene expression.
Dimethyl fumarate causes short-lived oxidative stress, which leads to increased levels and nuclear localization of the transcription factor nuclear factor erythroid 2-related factor 2 and a subsequent increase in glutathione synthesis and recycling in neuronal cells[1]. Dimethyl fumarate inhibits dendritic cell (DC) maturation by reducing inflammatory cytokine production (IL-12 and IL-6) and the expression of MHC class II, CD80, and CD86. Dimethyl fumarate impairs nuclear factor κB (NF-κB) signaling via reduced p65 nuclear translocalization and phosphorylation. Dimethyl fumarate inhibits maturation of DCs and subsequently Th1 and Th17 cell differentiation by suppression of both NF-κB and ERK1/2-MSK1 signaling[2]. Dimethyl fumarate inhibits TNF-alpha-induced nuclear entry of NF-kappaB in rat heart endothelial cells (RHEC)[3]. Dimethyl fumarate, an immune modulator and inducer of the antioxidant response, suppresses HIV replication and neurotoxin release. Dimethyl fumarate attenuates CCL2-induced monocyte chemotaxis, suggesting that Dimethyl fumarate could decrease recruitment of activated monocytes to the CNS in response to inflammatory mediators[4].
Dimethyl fumarate inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemia and reperfusion in rats in vivo[3]. Dimethyl fumarate oral administration is shown to upregulate mRNA and protein levels of Nrf2 and Nrf2-regulated cytoprotective genes, attenuate 6-OHDA induced striatal oxidative stress and inflammation in C57BL/6 mice[5].
References:
[1]. Albrecht P, et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012 Jul 7;9:163
[2]. Peng H, et al. Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor κB (NF-κB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling. J Biol Chem. 2012 Aug 10;287(33):28017-26.
[3]. Meili-Butz S, et al. Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats. Eur J Pharmacol. 2008 May 31;586(1-3):251-8.
[4]. Cross SA, et al. Dimethyl fumarate, an immune modulator and inducer of the antioxidant response, suppresses HIV replication and macrophage-mediated neurotoxicity: a novel candidate for HIV neuroprotection. J Immunol. 2011 Nov 15;187(10):5015-25.
[5]. Jing X, et al. Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity. Neuroscience. 2015 Feb 12;286:131-40
[6]. Li Y, et al. Dimethyl fumarate accelerates wound healing under diabetic condition. J Mol Endocrinol. 2018 Jul 23. pii: JME-18-0102.
|
Animal experiment: |
In a blinded design, the rats are assigned to one of the three experimental groups: a) to the DMF group receiving 10 mg/kg body weight DMF (dissolved in DMSO 2% in water), or b) to the vehicle group receiving only the vehicle (DMSO 2% in water; necessary to dissolve DMF), or c) to the positive control group receiving the vehicle plus ischemic preconditioning (IPC, known to reduce infarct size). This dose of 10 mg/kg body weight of DMF corresponded approximately to a maximally tolerated dose in man. As we could confirm in our in vitro experiments that DMF is the active compound, the in vivo experiments are performed with DMF but not with MHF. DMF and the vehicle, respectively, tail vein is administrated by i.v. 90 min before ischemia (under general anesthesia using isoflurane) as well as immediately before ischemia. Ischemic preconditioning is induced by two times 5 min episodes ischemia (induced by left coronary artery occlusion) each followed by 5 min of reperfusion (induced by releasing the snare). The experiments are performed (except pilot experiments) pair wise, i.e. two experiments in parallel avoiding identical group assignment. The present study are set up, and permitted to demonstrate a pharmacodynamic effect of DMF on myocardial infarct size in rats in vivo. An eventual mode of action should be investigated in vitro. The results from our in vitro experiments as well as results of other laboratories did not show any effect of MHF on NF-κB activation. Therefore, no experiment is included to exclude MHF from the mode of action of DMF. |
|
References: [1]. Albrecht P, et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012 Jul 7;9:163 |
|
| Cas No. | 624-49-7 | SDF | |
| 别名 | 富马酸二甲酯 | ||
| 化学名 | dimethyl (E)-but-2-enedioate | ||
| Canonical SMILES | COC(=O)C=CC(=O)OC | ||
| 分子式 | C6H8O4 | 分子量 | 144.13 |
| 溶解度 | ≥ 7.1mg/mL in DMSO | 储存条件 | Store at RT |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 6.9382 mL | 34.6909 mL | 69.3818 mL |
| 5 mM | 1.3876 mL | 6.9382 mL | 13.8764 mL |
| 10 mM | 0.6938 mL | 3.4691 mL | 6.9382 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。
Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet