Etomoxir-R-plus-Etomoxir-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEtomoxirCat. No.: HY-50202CAS No.: 124083-20-1Synonyms: (R)-(+)-Etomoxir分式: CHClO分量: 326.82作靶点: Others作通路: Others储存式: -20C, protect from light, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (protect fromlight

2、, stored under nitrogen)溶解性数据体外实验 DMSO : 50 mg/mL (152.99 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.65 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.65 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性

3、 Etomoxir (R)-(+)-Etomoxir)有效的毒碱棕榈酰转移酶-I (CPT-1) 的抑制剂。IC50 & Target CPT-1 1体外研究 Etomoxir binds irreversibly to the catalytic site of CPT-1 inhibiting its activity, but also upregulates fatty acidoxidation enzymes. Etomoxir is developed as an inhibitor of the mitochondrial carnitine palmitoyltransfer

4、ase-1 (CPT-1) located on the outer mitochondrial membrane. Etomoxir, in the liver can act as peroxisomalproliferator, increasing DNA synthesis and liver growth. Thus, etomoxir, in addition of being a CPT1 inhibitorcould be considered as a PPARalpha agonist 1. Etomoxir is a member of the oxirane carb

5、oxylic acidcarnitine palmitoyl transferase I inhibitors and has been suggested as a therapeutic agent for the treatment ofheart failure. Acute Etomoxir treatment irreversibly inhibits the activity of carnitine palmitoyltransferase I. As aresult, fatty acid import into the mitochondria and -oxidation

6、 is reduced, whereas cytosolic fatty acidaccumulates and glucose oxidation is elevated. Prolonged incubation (24 h) with Etomoxir produces diverseeffects on the expression of several metabolic enzyme 2.体内研究 Etomoxir is an inhibitor of free fatty acid (FFA) oxidation-related key enzyme CPT1. P53 inte

7、racts directly withBax, which is inhibited by Etomoxir, further confirming the direct interaction of P53 and Bax, and theinvolvement of FAO-mediated mitochondrial ROS generation in db/db mice 3. Rats are injected daily withEtomoxir, a specific CPT-I inhibitor, for 8 days at 20 mg/kg of body mass. Et

8、omoxir-treated rats display a44% reduced cardiac CPT-I activity. The treatment of Lewis rats for 8 days with 20 mg/kg Etomoxir does notalter blood glucose, which is in line with comparable etomoxir-feeding studies. Similarly, Etomoxir feedingdoes not affect general growth characteristics such as gai

9、n in body mass, nor does it affect hindlimb musclemass. However, heart mass and liver mass are both significantly increased by 11% in Etomoxir-treated rats4.PROTOCOLCell Assay 2 Rat heart H9c2 myoblastic cells are incubated in DMEM containing 10% fetal bovine serum until nearconfluence. In some expe

10、riments, cells are preincubated for 2 h with DMEM (serum-free) in the absence orpresence of 1-80 M Etomoxir and then incubated for 2 h with 0.1 mM 1-14Coleic acid (10 Ci/dish, bindsto BSA in a 1:1 molar ratio). In other experiments, cells are preincubated for 2 h plus or minus 40 MEtomoxir and then

11、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 in a 1:1 molar ratio), 0.1 mM 1-14Cpalmitic acid (2 Ci/dish, bindsto BSA in a 1:1 molar ratio), 28 M 3Hethanolamine (2 Ci/dish), 28 M methyl-3Hcholine (2 Ci/dish), 0.4mM 3Hserine (20 C

12、i/dish), or 40 M myo-3Hinositol (10 Ci/dish). The medium is removed and the cellswashed twice with ice-cold saline and then harvested from the dish with 2 mL methanol-water (1:1, v/v) forlipid extraction. An aliquot of the homogenate is taken for the determination of total uptake of radioactivity in

13、tocells. Phospholipids are then isolated and radioactivity in these determined 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAnimal Mice 3Administration 34 80 male C57BLKS/J lar-Leprdb/db mice and 20

14、wild type littermates (8 week) are used. db/db mice arerandomly divided into four groups: db/db group, Etomoxir group, MitoQ group, and PFT- group. In theEtomoxir group, mice are intraperitoneally injected with 1 mg/kg Etomoxir twice every week. In the MitoQgroup, 50 M MitoQ is given to the mice in

15、water. Water bottles, containing either MitoQ, are covered withaluminum foil, and all bottles are refilled every 3 days. In the PFT- group, mice are intraperitoneally injectedwith 1 mg/kg PFT- twice every week. WT mice are administrated with vehicle instead. The experimentalperiod is 8 weeks. At the

16、 end, peripheral blood samples and bone marrow cells are harvested for the assays.Rats 4Male Lewis rats, weighing 150-200 g, are used in the present study. Animals are kept on a 12 h:12 hlight/dark cycle and fed a Purina Chow diet and water ad libitum. The rats are divided into two groups: (1)contro

17、l and (2) Etomoxir. Etomoxir (20 mg/kg of body weight) is dissolved in 0.9% (w/v) NaCl andadministered intraperitoneally for 8 days. Control rats receive saline. The last injection is given 24 h beforethe experiment. Animals are anaesthetized with an intraperitoneal injection of a nembutal and hepar

18、in (3:1)mixture. Subsequently, the heart is removed for LCFA uptake studies and for analyses of transporter proteincontents.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 Bi

19、ol. 2018 Oct;19:412-428. Redox Biol. 2018 Jul;17:180-191. Free Radical Bio Med. 2019 Jul.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Rupp H, et al. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002Nov;27(7):621-36.2. Xu FY, et al. Etomoxir mediates differential metabolic channeling of fatty acid and glycerol precursors into cardiolipin in H9c