| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
R-(+)-Etomoxir, R-isomer of etomoxir, is a novel and potent inhibitor of CPT1 (carnitine palmitoyltransferase A), which is required for the oexidation of long-chain acyl CoA esters. Etomoxir is an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) on the outer face of the inner mitochondrial membrane. It inhibits β-oxidation in mitochondria; shown to inhibit cardiolipin biosynthesis from exogenous fatty acid in H9c2 cells. Etomoxir has also been identified as a direct agonist of PPARα. Etomoxir is a compound that binds irreversibly to the catalytic site of CPT-1 inhibiting its activity, but also upregulates fatty acid oxidation enzymes.
| Targets |
Carnitine palmitoyltransferase I (CPT-I)
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|---|---|
| ln Vitro |
In H9c2 cells, etomoxir facilitates the distinct metabolic channeling of fatty acid and glycerol precursors into cardiolipin[2]. Although etomoxir reduces the incorporation of [1-14C]palmitic acid or [1-14C]oleic acid into cardiolipin, it has no effect on the activity of the enzymes involved in the biosynthesis and remodeling of cardiolipin[2]. Cardiolipin's incorporation of [1,3-3H]glycerol is increased by etomoxir. The process involves a 33% rise in glycerol kinase activity, which causes an increase in glycerol flux via the cardiolipin biosynthesis de novo pathway [2].
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| Enzyme Assay |
shRNA-GFP lentiviral plasmid construction and infection[1]
The puromycin resistance gene in 5 individual shRNA lentiviral plasmids against CPT1A was replaced with GFP cDNA using standard molecular biology techniques. Briefly, a 1.4 kb GFP cDNA insert was subcloned from the lentiviral PELPS-GFP plasmid into KpnΙ and BamHΙ sites in the pLKO.1 shRNA plasmid. The efficacy of each individual lentiviral plasmid was determined by immunoblot analysis. Lentiviral infections were performed as described36. Lymphocytes expressing shRNA against CPT1A were compared with the corresponding control plasmid that we also engineered to express GFP instead of puromycin resistance. The control plasmid encoded a scrambled shRNA sequence from the human β-actin gene. The efficiency of lentiviral infection ranged from 60–90% across experiments. In assessments of cell proliferation, enumeration was performed using bead-based counting methods following gating on GFP + cells. The titers for scramble-GFP and shRNA-CPT1A-GFP viral supernatants were 9.45e6 and 7.34e6 TU/ml, respectively.[1]
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| Animal Protocol |
80 male C57BLKS/J lar-Leprdb/db mice and 20 wild type littermates (8 week) were obtained from Model Animal Research Centre, Nanjing University, China. Mice were housed in cages in a limited access room, under temperature (23 ± 2 °C) and humidity (55 ± 5%) condition with a standard light (12 h light/dark) cycle and fed a regular diet. db/db mice were randomly divided into four groups: db/db group, Etomoxir group, MitoQ group, and PFT-α group. In the Etomoxir group, mice were intraperitoneally injected with 1 mg/kg Etomoxir twice every week. In the MitoQ group, 50 μmol/L MitoQ was given to the mice in water. Water bottles, containing either MitoQ, were covered with aluminum foil, and all bottles were refilled every 3 days. In the PFT-α group, mice were intraperitoneally injected with 1 mg/kg PFT-α twice every week. WT mice were administrated with vehicle instead. The experimental period is 8 weeks. At the end, peripheral blood samples and bone marrow cells were harvested for the assays. 100 C57BL/6 mice obtained from Experimental Animal Centre of Fourth Military Medical University. The mice were randomly divided into five groups: Control group, HF diet group, Etomoxir group, MitoQ group, and PFT-α group. Mice in HF diet, Etomoxir, MitoQ, and PFT-α groups were given high fat diet for 20 weeks and mice in Etomoxir, MitoQ, and PFT-α groups were administrated with Etomoxir, MitoQ, and PFT-α in the last 10 weeks. The administration of Etomoxir, MitoQ, and PFT-α were identical to the treatment in db/db mice. Control mice were administrated with vehicle instead [3].
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| References |
|
| Molecular Formula |
C15H18CLKO4
|
|---|---|
| Molecular Weight |
336.85200
|
| Exact Mass |
336.053
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| Elemental Analysis |
C, 53.48; H, 5.39; Cl, 10.52; K, 11.61; O, 19.00
|
| CAS # |
132308-39-5
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| Related CAS # |
828934-41-4 (sodium); 82258-36-4 (racemate); 828934-40-3 (S-isomer); 132308-39-5 (R-isomer potassium); 124083-20-1
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| PubChem CID |
23706479
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.188
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
21
|
| Complexity |
321
|
| Defined Atom Stereocenter Count |
1
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| SMILES |
[K+].ClC1=CC=C(OCCCCCC[C@@]2(CO2)C([O-])=O)C=C1
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| InChi Key |
WBBGJSPIXZAHCU-XFULWGLBSA-M
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| InChi Code |
InChI=1S/C15H19ClO4.K/c16-12-5-7-13(8-6-12)19-10-4-2-1-3-9-15(11-20-15)14(17)18/h5-8H,1-4,9-11H2,(H,17,18)/q+1/p-1/t15-/m1./s1
|
| Chemical Name |
(R)-2-[6-(4-Chlorophenoxy)hexyl]oxiranecarboxylic Acid Potassium Salt
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| Synonyms |
R-(+)-Etomoxir Carboxylate, Potassium Salt
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9687 mL | 14.8434 mL | 29.6868 mL | |
| 5 mM | 0.5937 mL | 2.9687 mL | 5.9374 mL | |
| 10 mM | 0.2969 mL | 1.4843 mL | 2.9687 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03144128 | COMPLETED | Dietary Supplement: Vitamin D Dietary Supplement: Placebo |
Cancer Cachexia Vitamin D Deficiency |
David Travis Thomas | 2018-05-23 | Not Applicable |
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