乙莫克舍作用机制 - Medchemexpress - MCE中国

1、Product Data SheetEtomoxirCat. No.: HY-50202CAS No.: 124083-20-1分式: CHClO分量: 326.82作靶点: Apoptosis作通路: Apoptosis储存式: -20C, protect from light, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (protect from light, stored undernitrogen)溶解性数据体外实验 DMSO : 50 mg/mL (152.99 mM)H2O : 0.1 mg/

2、mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 3.0598 mL 15.2989 mL 30.5979 mL5 mM 0.6120 mL 3.0598 mL 6.1196 mL10 mM 0.3060 mL 1.5299 mL 3.0598 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month (p

3、rotect from light, stored under nitrogen)。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80

4、45% salineSolubility: 2.5 mg/mL (7.65 mM); Clear solution此案可获得 2.5 mg/mL (7.65 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.65 mM); Clear solutionPage 1 of

5、2 www.MedChemE此案可获得 2.5 mg/mL (7.65 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Etomoxir (R)-(+)-Etomoxir)碱棕榈酰转移酶 1a (CPT-1a) 抑制剂，通过抑制 CPT-1a 可抑制脂 酸氧化，并抑制、和豚中棕榈酸酯的氧化。IC & Target CPT-1a5体外研究 Etomoxir binds irreversibly to the ca

6、talytic site of CPT-1 inhibiting its activity, but also upregulates fatty acid oxidationenzymes. Etomoxir is developed as an inhibitor of the mitochondrial carnitine palmitoyltransferase-1 (CPT-1) locatedon the outer mitochondrial membrane. Etomoxir, in the liver can act as peroxisomal proliferator,

7、 increasing DNAsynthesis and liver growth. Thus, etomoxir, in addition of being a CPT1 inhibitor could be considered as a PPARalphaagonist1. Etomoxir is a member of the oxirane carboxylic acid carnitine palmitoyl transferase I inhibitors and hasbeen suggested as a therapeutic agent for the treatment

8、 of heart failure. Acute Etomoxir treatment irreversiblyinhibits the activity of carnitine palmitoyltransferase I. As a result, fatty acid import into the mitochondria and -oxidation is reduced, whereas cytosolic fatty acid accumulates and glucose oxidation is elevated. Prolongedincubation (24 h) wi

9、th Etomoxir produces diverse effects on the expression of several metabolic enzyme2.体内研究 Etomoxir is an inhibitor of free fatty acid (FFA) oxidation-related key enzyme CPT1. P53 interacts directly with Bax,which is inhibited by Etomoxir, further confirming the direct interaction of P53 and Bax, and

10、the involvement of FAO- mediated mitochondrial ROS generation in db/db mice3. Rats are injected daily with Etomoxir, a specific CPT-Iinhibitor, for 8 days at 20 mg/kg of body mass. Etomoxir-treated rats display a 44% reduced cardiac CPT-I activity.The treatment of Lewis rats for 8 days with 20 mg/kg

11、 Etomoxir does not alter blood glucose, which is in line withcomparable etomoxir-feeding studies. Similarly, Etomoxir feeding does not affect general growth characteristics suchas gain in body mass, nor does it affect hindlimb muscle mass. However, heart mass and liver mass are bothsignificantly inc

12、reased by 11% in Etomoxir-treated rats4.PROTOCOLCell Assay 2 Rat heart H9c2 myoblastic cells are incubated in DMEM containing 10% fetal bovine serum until near confluence. Insome experiments, cells are preincubated for 2 h with DMEM (serum-free) in the absence or presence of 1-80 MEtomoxir and then

13、incubated for 2 h with 0.1 mM 1-14Coleic acid (10 Ci/dish, binds to BSA in a 1:1 molar ratio). Inother experiments, cells are preincubated for 2 h plus or minus 40 M Etomoxir and then incubated for 2 h with 0.1 M or 0.1 mM 1,3-3Hglycerol (10 Ci/dish), 0.1 mM 1-14Coleic acid (2 Ci/dish, binds to BSA

14、in a 1:1 molar ratio),0.1 mM 1-14Cpalmitic acid (2 Ci/dish, binds to BSA in a 1:1 molar ratio), 28 M methyl-3Hcholine (2 Ci/dish), 0.4mM 3Hserine (20 Ci/dish), or 40 M myo-3Hinositol (10 Ci/dish). The medium is removed and the cells washedtwice with ice-cold saline and then harvested from the dish w

15、ith 2 mL methanol-water (1:1, v/v) for lipid extraction.An aliquot of the homogenate is taken for the determination of total uptake of radioactivity into cells. Phospholipidsare then isolated and radioactivity in these determined2.MCE has not independently confirmed the accuracy of these methods. Th

16、ey are for reference only.Animal Mice3Administration 34 80 male C57BLKS/J lar-Leprdb/db mice and 20 wild type littermates (8 week) are used. db/db mice are randomlydivided into four groups: db/db group, Etomoxir group, MitoQ group, and PFT- group. In the Etomoxir group, miceare intraperitoneally inj

17、ected with 1 mg/kg Etomoxir twice every week. In the MitoQ group, 50 M MitoQ is given toPage 2 of 3 www.MedChemEthe mice in water. Water bottles, containing either MitoQ, are covered with aluminum foil, and all bottles are refilledevery 3 days. In the PFT- group, mice are intraperitoneally injected

18、with 1 mg/kg PFT- twice every week. WT miceare administrated with vehicle instead. The experimental period is 8 weeks. At the end, peripheral blood samples andbone marrow cells are harvested for the assays.Rats4Male Lewis rats, weighing 150-200 g, are used in the present study. Animals are kept on a

19、 12 h:12 h light/dark cycleand fed a Purina Chow diet and water ad libitum. The rats are divided into two groups: (1) control and (2) Etomoxir.Etomoxir (20 mg/kg of body weight) is dissolved in 0.9% (w/v) NaCl and administered intraperitoneally for 8 days.Control rats receive saline. The last inject

20、ion is given 24 h before the experiment.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Cell Metab. 2018 Oct. Cell Rep. 2019 Apr 2;27(1):226-237.e4. Redox Biol. 2018 Oct;19:412-428. Redox Biol. 2018 Jul;17:180-191. Free Radic Biol Med. 2019

21、Sep;141:372-382.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Rupp H, et al. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002 Nov;27(7):621-36.2. Xu FY, et al. Etomoxir mediates differential metabolic channeling of fatty acid and glycerol precursors into cardiolipin in H9c2 cells. J Lipid Res. 2003Feb;44(2):415-23.3. Li J, et al. FFA-ROS-P53-mediated mitochondrial apopt