Oxidation of long-chain fatty acids inside of the mitochondrial matrix provides an essential source of energy for some cells. Since long-chain fatty acids cannot freely pass into the mitochondrial matrix, they rely on a protein called carnitine palmitoyltransferase I (CPT1) for transport. CPT1 has been identified as a potential therapeutic target for a growing list of cancers that include breast cancer, prostate cancer, glioblastoma, colon cancer, gastric cancer, myeloma, and others[3]. (R)-(+)-etomoxir sodium salt is an inhibitor of carnitine palmitoyltransferase I (CPT1). Etomoxir at 10-6 M prevented the palmitate-induced depression of function in heart but did not decrease myocardial long chain acylcarnitine or long chain acyl-CoA levels, and oxygen consumption per unit work was decreased during reperfusion recovery, and ATP and creatine-phosphate levels were significantly higher after reperfusion[4]. 200 μM of etomoxir caused a significant reduction in cellular proliferation rate in BT549 cells, while 10 μM did not. 200 μM etomoxir treatment, however, significantly impaired mitochondrial respiration in BT549 cells, and a 65% decrease in basal respiration and a 65% decrease in maximal respiratory capacity after treating cells with 200 μM etomoxir was measured[3]. Non-insulin-dependent diabetes mellitus (NIDDM) patients who received oral etomoxir treatment twice daily at the dose of 25 mg to 100 mg showed dose-dependent decrease in fasting blood glucose[5].
Etomoxir sodium salt/乙莫克舍钠盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MDSCs
4 μM
3 h
To inhibit fatty acid oxidation and evaluate its impact on the metabolism and function of MDSCs.
Cell Metab. 2022 May 3;34(5):761-774.e9.
Endothelial Cells
Etomoxir inhibited mitochondrial long-chain fatty acid oxidation (FAO) and reduced endothelial cell proliferation, but did not affect their migration.
Nature. 2015 Apr 9;520(7546):192-197.
NK cells
150 µM
3 and 6 h
Inhibited fatty acid oxidation, significantly suppressing the respiration of IL-10 stimulated NK cells
Front Immunol. 2021 Feb 23;12:619195.
BMDMs
5µM
18h
Inhibition of fatty acid oxidation to restore TNF and IL-6 production
To investigate the effect of Etomoxir on food intake, results showed that 24 hours after Etomoxir treatment, food intake in transgenic mice increased and normalized to the level of the vehicle and inhibitor-treated negative littermates.
Diabetes. 2012 May;61(5):1122-32
Mice
C57BL/6 mice
Intraperitoneal injection
20 mg/kg
24 hours prior to infection and on the day of infection
To evaluate the effect of Etomoxir on the metabolic and immune responses in MKP103-infected mice, results showed increased bacterial loads and enhanced inflammatory responses in Etomoxir-treated mice.
Cell Metab. 2022 May 3;34(5):761-774.e9.
Mice
OVA or HDM-induced asthma models
Intraperitoneal injection
50 mg/kg
Two injections, 24 hours apart
Etomoxir significantly decreased allergen-induced airway hyperresponsiveness, reduced the number of inflammatory cells, and decreased the production of cytokines and chemokines associated with asthma.
Clin Exp Allergy. 2017 Sep;47(9):1170-1184
Mice
C57BL/6 wild type mice
Intraperitoneal injection
30-35 mg/kg
Once daily from P2 to P4
Etomoxir inhibited FAO, causing retinal vascular defects in mice and reducing pathological angiogenesis in a model of retinopathy of prematurity (ROP).
Nature. 2015 Apr 9;520(7546):192-197.
Mice
Hyperglycemia-induced suppression of physiological retinal vessel growth model
Intraperitoneal injection
4 mg/kg
Once daily from P7 to P9
Etomoxir significantly attenuated the promotion of physiological retinal vessel growth by FGF21 through inhibition of mitochondrial fatty acid oxidation.
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