In cells treated with eicosapentaenoic acid (EPA; 100 μM; 24 hours), the phosphorylated form of C/EBPβ was significantly visible, while it was hardly noticeable in control and OA or LA-treated U937 cells [1]. H-Ras and N-Ras mRNA levels significantly increased after 1, 3, and 24 hours and continued after 1 to 3 hours. Eicosapentaenoic acid has no effect on the levels of K-Ras mRNA [1].

Metabolism / Metabolites
Eicosapentaenoic acid has known human metabolites that include Juniperonic acid.

[1]. Martins, J.G., EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr, 2009. 28(5): p. 525-42.

[2]. Dietary ω-3 polyunsaturated fatty acids are protective for myopia. Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2104689118.

[3]. Endogenous omega-3 long-chain fatty acid biosynthesis from alpha-linolenic acid is affected by substrate levels, gene expression, and product inhibition. RSC Adv., 2017, 7, 40946-40951.

All-cis-5,8,11,14,17-icosapentaenoic acid is an icosapentaenoic acid having five cis-double bonds at positions 5, 8, 11, 14 and 17. It has a role as a nutraceutical, a micronutrient, an antineoplastic agent, an antidepressant, a Daphnia galeata metabolite, a mouse metabolite, an anticholesteremic drug and a fungal metabolite. It is an icosapentaenoic acid and an omega-3 fatty acid. It is a conjugate acid of an all-cis-5,8,11,14,17-icosapentaenoate.
Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.
Eicosapentaenoic acid has been reported in Mortierella alpina, Tornabea scutellifera, and other organisms with data available.
Icosapent is the free fatty acid (FFA) form of eicosapentaenoic acid (EPA), a polyunsaturated long-chain fatty acid found in fish oil with a 20-carbon backbone and 5 double bonds, with potential supplementing, anti-inflammatory, anti-thrombotic, immunomodulating, anti-angiogenic and chemopreventive activities. Upon administration of icosapent, the free form of EPA is incorporated in cell membrane phospholipids and replaces arachidonic acid. This inhibits arachidonic acid conversion into thromboxanes and prostaglandin E2 (PGE2). Upon oral administration of icosapent, the EPA-FFA prevents and suppresses colonic neoplasia and reduces polyp formation and growth through as of yet not fully elucidated mechanisms.
Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.
See also: Icosapent Ethyl (active moiety of); Fish Oil (is active moiety of); Eicosapentaenoic Acid (subclass of) ... View More ...

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Drug Indication
EPA can be used for lowering elevated triglycerides in those who are hyperglyceridemic. In addition, EPA may play a therapeutic role in patients with cystic fibrosis by reducing disease severity and may play a similar role in type 2 diabetics in slowing the progression of diabetic nephropathy.
FDA Label
Treatment of Familial Adenomatous Polyposis

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Mechanism of Action
The anti-inflammatory, antithrombotic and immunomodulatory actions of EPA is probably due to its role in eicosanoid physiology and biochemistry. Most eicosanoids are produced by the metabolism of omega-3 fatty acids, specifically, arachidonic acid. These eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2) stimulate leukocyte chemotaxis, platelet aggregation and vasoconstriction. They are thrombogenic and artherogenic. On the other hand, EPA is metabolized to leukotriene B5 (LTB5) and thromboxane A3 (TXA3), which are eicosanoids that promote vasodilation, inhibit platelet aggregation and leukocyte chemotaxis and are anti-artherogenic and anti-thrombotic. The triglyceride-lowering effect of EPA results from inhibition of lipogenesis and stimulation of fatty acid oxidation. Fatty acid oxidation of EPA occurs mainly in the mitochondria. EPA is a substrate for Prostaglandin-endoperoxide synthase 1 and 2. It also appears to affect the function and bind to the Carbohydrate responsive element binding protein (ChREBP) and to a fatty acid receptor (G-coupled receptor) known as GP40.

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Pharmacodynamics
Eicosanoids are chemical messengers derived from 20-carbon polyunsaturated fatty acids that play critical roles in immune and inflammatory responses. Both 20-carbon omega-6 fatty acids (arachidonic acid) and 20-carbon omega-3 fatty acids (EPA) can be found in cell membranes. During an inflammatory response, arachidonic acid and EPA are metabolized by enzymes known as cyclooxygenases and lipoxygenases to form eicosanoids. Increasing omega-3 fatty acid intake increases the EPA content of cell membranes and decreases the arachidonic acid content, resulting in higher proportions of eicosanoids derived from EPA. Physiologic responses to arachidonic acid-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and clotting than eicosanoids derived from arachidonic acid.

C20H30O2

302.451

302.224

10417-94-4

Eicosapentaenoic Acid-d5;1197205-73-4;Eicosapentaenoic acid ethyl ester;86227-47-6;Eicosapentaenoic Acid sodium;73167-03-0

446284

Colorless to light yellow liquid

0.9±0.1 g/cm3

439.3±24.0 °C at 760 mmHg

-54--53ºC(lit.)

336.0±18.0 °C

0.0±2.3 mmHg at 25°C

1.513

6.23

1

2

13

22

398

0

CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(O)=O

JAZBEHYOTPTENJ-JLNKQSITSA-N

InChI=1S/C20H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13,15-16H,2,5,8,11,14,17-19H2,1H3,(H,21,22)/b4-3-,7-6-,10-9-,13-12-,16-15-

(5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoic acid

EPA. Icosapent, Eicosapentaenoic acid, Timnodonic acid, Vascepa, Epadel, EPAX

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol :≥ 100 mg/mL (~330.63 mM)
DMSO : ≥ 30 mg/mL (~99.19 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.08 mg/mL (6.88 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 2.08 mg/mL (6.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.08 mg/mL (6.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)