富馬酸二甲酯作用機制 - Medchemexpress - MCE中國

1、Product Data SheetDimethyl fumarateCat. No.: HY-17363CAS No.: 624-49-7分式: CHO分量: 144.13作靶點: Keap1-Nrf2; Endogenous Metabolite作通路: NF-B; Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (346.91 mM; Need ultrasonic)SolventMass1 mg

2、 5 mg 10 mgConcentration制備儲備液1 mM 6.9382 mL 34.6909 mL 69.3818 mL5 mM 1.3876 mL 6.9382 mL 13.8764 mL10 mM 0.6938 mL 3.4691 mL 6.9382 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?。以下溶解案都請?/p>

3、按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (17.35 mM); Clear solution此案可獲得 2.5 mg/mL (17.35 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 1

4、00 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (17.35 mM); Clear solution此案可獲得 2.5 mg/mL (17.35 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲

5、備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (17.35 mM); Clear solution此案可獲得 2.5 mg/mL (17.35 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Dimethyl fumarate種 Nrf2 激活劑，能夠誘導上調(diào)抗氧化基因的表達。IC

6、 & Target Human Endogenous Metabolite(批量添加)體外研究 Dimethyl fumarate causes short-lived oxidative stress, which leads to increased levels and nuclear localization of thetranscription factor nuclear factor erythroid 2-related factor 2 and a subsequent increase in glutathione synthesis andrecycling in ne

7、uronal cells1. Dimethyl fumarate inhibits dendritic cell (DC) maturation by reducing inflammatorycytokine production (IL-12 and IL-6) and the expression of MHC class II, CD80, and CD86. Dimethyl fumarate impairsnuclear factor B (NF-B) signaling via reduced p65 nuclear translocalization and phosphory

8、lation. Dimethyl fumarateinhibits maturation of DCs and subsequently Th1 and Th17 cell differentiation by suppression of both NF-B andERK1/2-MSK1 signaling2. Dimethyl fumarate inhibits TNF-alpha-induced nuclear entry of NF-kappaB in rat heartendothelial cells (RHEC)3. Dimethyl fumarate, an immune mo

9、dulator and inducer of the antioxidant response,suppresses HIV replication and neurotoxin release. Dimethyl fumarate attenuates CCL2-induced monocytechemotaxis, suggesting that Dimethyl fumarate could decrease recruitment of activated monocytes to the CNS inresponse to inflammatory mediators4.體內(nèi)研究 D

10、imethyl fumarate inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemiaand reperfusion in rats in vivo3. Dimethyl fumarate oral administration is shown to upregulate mRNA and proteinlevels of Nrf2 and Nrf2-regulated cytoprotective genes, attenuate 6-OHDA induc

11、ed striatal oxidative stress andinflammation in C57BL/6 mice5.PROTOCOLAnimal In a blinded design, the rats are assigned to one of the three experimental groups: a) to the DMF group receiving 10Administration 3 mg/kg body weight DMF (dissolved in DMSO 2% in water), or b) to the vehicle group receivin

12、g only the vehicle(DMSO 2% in water; necessary to dissolve DMF), or c) to the positive control group receiving the vehicle plusischemic preconditioning (IPC, known to reduce infarct size). This dose of 10 mg/kg body weight of DMFcorresponded approximately to a maximally tolerated dose in man. As we

13、could confirm in our in vitro experimentsthat DMF is the active compound, the in vivo experiments are performed with DMF but not with MHF. DMF and thevehicle, respectively, tail vein is administrated by i.v. 90 min before ischemia (under general anesthesia usingisoflurane) as well as immediately bef

14、ore ischemia. Ischemic preconditioning is induced by two times 5 min episodesischemia (induced by left coronary artery occlusion) each followed by 5 min of reperfusion (induced by releasing thesnare). The experiments are performed (except pilot experiments) pair wise, i.e. two experiments in paralle

15、l avoidingidentical group assignment. The present study are set up, and permitted to demonstrate a pharmacodynamic effectof DMF on myocardial infarct size in rats in vivo. An eventual mode of action should be investigated in vitro. Theresults from our in vitro experiments as well as results of other

16、 laboratories did not show any effect of MHF on NF-Bactivation. Therefore, no experiment is included to exclude MHF from the mode of action of DMF.Page 2 of 3 www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Aging (Albany NY). 201

17、8 Aug 16;10(8):2016-2036. J Mol Endocrinol. 2018 Oct 15;61(4):163-172.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Albrecht P, et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012 Jul 7;9:1632. Peng H, et al. Dimet

18、hyl fumarate inhibits dendritic cell maturation via nuclear factor B (NF-B) 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

19、 psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats. EurJ 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 candi