Phospholipid

ETC-588, also known as LUV (large monolayer vesicle), is composed of natural lipids and circulates in arteries, promoting the clearance of cholesterol and other lipids accumulated in cells, including arterial wall cells, by high-density lipoprotein (HDL). LUVs transport excess cholesterol from the vascular system to the liver, where it is ultimately eliminated via the reverse lipid transport (RLT) pathway. It is believed that ETC-588's cholesterol clearance through this pathway may reverse atherosclerosis. Esperion is currently developing ETC-588 for the treatment of patients with acute coronary syndrome.

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Drug Indications
Studied for the treatment of atherosclerosis, coronary artery disease, and vascular disease.

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Mechanism of Action
ETC-588 is a phospholipid bilayer that chelates cholesterol. High-density lipoprotein (HDL) particles are small enough to penetrate the arterial wall, and once they have extracted cholesterol from plaque, they rapidly transfer it to monolayer vesicles (LUVs). The LUVs then transport the cholesterol to the liver for processing.

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Drug Indications
Studied for the treatment of atherosclerosis, coronary artery disease, and vascular disease.
Therapeutic Uses
Surfactant
/EXPL THER/ Endosulfan is a common organochlorine pesticide found in aquatic environments and has been found to reduce the heat tolerance of fish. Lipid-stimulating agents such as lecithin have been shown to improve the heat tolerance of fish. This study aimed to evaluate the role of a lipid-stimulating agent (lecithin) in improving the heat tolerance of haddock (Chanos chanos) under sublethal low-dose endosulfan-induced stress. 225 fish were randomly assigned to 5 treatment groups, with 3 replicates per treatment group. Four isocaloric and isonitrogenous diets were prepared, with different concentrations of lecithin added: normal water + control diet (En0/L0), endosulfan-treated water + control diet (En/L0), and endosulfan-treated water + diets supplemented with 1% (En/L1%), 1.5% (En/L1.5%), and 2% (En/L2%) lecithin, respectively. The endosulfan concentration in the treated water was maintained at 1/40 of the LC50 (0.52 ppb). After 5 weeks, the critical maximum temperature (CTmax), lethal maximum temperature (LTmax), critical minimum temperature (CTmin), and lethal minimum temperature (LTmin) were measured. Compared with the control group and the endosulfan-exposed group, the temperature tolerance (CTmax, LTmax, CTmin, and LTmin) of animals fed diets supplemented with 1%, 1.5%, and 2% lecithin were significantly improved (P<0.01). Positive correlations were found between CTmax and LTmax (R²=0.934) and between CTmin and LTmin (R²=0.9313). At the end of the heat tolerance study, feeding with lecithin significantly improved changes in endosulfan-induced cellular stress kinases (catalase, superoxide dismutase, and glutathione S-transferase in the liver and gills, and the neurotransmitter enzyme acetylcholinesterase in the brain) (p<0.01). This paper reports the role of lecithin in enhancing heat tolerance and protecting fish exposed to organochlorine pesticides from cellular stress. PMID:25455939
/EXPL THER/ The suitability of liquid lecithin (i.e., a solution of lecithin in soybean oil with a phospholipid content of approximately 60% w/w) for gel formation after the addition of poloxamer 407 aqueous solution was investigated, and the formulated system was evaluated as a carrier for transdermal ibuprofen administration. Formulation studies were conducted on a lecithin/poloxamer 407/water ternary system under a constant lecithin/poloxamer 407 mass ratio of 2.0. The results showed that the minimum concentrations of lecithin and poloxamer 407 required to form a gel-like system were 15.75% (w/w) and 13.13% (w/w), respectively, while the maximum water content was 60.62% (w/w). Systems with water content ranging from 55% to 60.62% (w/w) were soft semi-solids suitable for topical applications and were selected for physicochemical and biopharmaceutical evaluation. Conductivity analysis and optical microscopy observations indicated that the studied system was a water-soluble dispersion of spherical oligomeric layered assemblages formed by phospholipid and triglyceride molecules in an aqueous copolymer solution. Rheological behavior evaluation results indicated that the studied gel was a thermosensitive shear-thinning system. Ibuprofen (5% w/w) was dispersed in a pre-prepared carrier. The drug delivery system was stable for 30 days at storage temperatures ranging from 5 ± 3 °C to 40 ± 2 °C. In vitro ibuprofen release conformed to the Higuchi model (rH>0.95) and was sustained for 12 hours. These results indicate that the optimized LLPBG formulation, with optimized drug release and sensory properties, holds promise as a carrier for sustained transdermal administration of poorly soluble drugs. PMID:26002567
/EXPL THER/ Some dietary factors may inhibit lead poisoning. This study aimed to evaluate the effects of dietary compounds rich in unsaturated fatty acids (FA) on blood lead levels, lipid metabolism, and vascular reactivity in rats. The possible mechanisms by which unsaturated fatty acids affect blood lead levels were explored by detecting serum metallothionein and organ lead levels. Male Wistar rats, who drank lead-containing (100 ppm Pb) or lead-free acetate-free drinking water for three months, were orally supplemented daily with either virgin olive oil or flaxseed oil (0.2 mL/kg body weight) or the lecithin component "Super Lecithin" (50 g/kg body weight). In in vitro experiments, mesenteric arteries were stimulated with six different doses of norepinephrine (NE). Lecithin supplementation slightly reduced the arterial pressor response to NE. Lead supplementation in rats weakened the beneficial effects of unsaturated fatty acids on lipid metabolism and vascular response to adrenergic stimulation. On the other hand, super lecithin and flaxseed oil with a low ω-6/ω-3 ratio (approximately 1) reduced blood lead levels. This effect was observed in both lead-poisoned rats (p < 0.0001) and non-lead-poisoned rats (p < 0.05). PMID: 26075218
Pharmacodynamics
ETC-588, also known as LUV (large monolayer vesicle), is composed of naturally occurring lipids that circulate in arteries to promote the clearance of cholesterol and other lipids accumulated in cells, including arterial wall cells, by high-density lipoprotein (HDL). LUVs transport excess cholesterol from the vascular system to the liver, where it is ultimately excreted via the reverse lipid transport (RLT) pathway.
Biological Essentiality: An important component of nerve tissue and brain parenchyma. ETC-588 is a mixture of diglycerides of stearic acid, palmitic acid, and oleic acid linked to phosphocholine esters.
Mechanism of Action
ETC-588 is a phospholipid bilayer capable of chelating cholesterol. Once sufficiently small HDL particles can penetrate the arterial wall and absorb cholesterol from plaque, it rapidly transfers the cholesterol to the LUV. The LUV then transports the cholesterol to the liver for processing.

C42H82NO8P

760.076155185699

759.577

8057-53-2

8057-53-2 (from egg yolk);8002-43-5 (from Soybean);

6449792

Typically exists as solid at room temperature

13.6

0

8

41

52

899

0

CCCCCCCCCCCCCCCC(=O)OC(COC(=O)CCCCCCC/C=C\CCCCCCCC)COP(=O)([O-])OCC[N+](C)(C)C

RRVPPYNAZJRZFR-MRCUWXFGSA-N

InChI=1S/C42H82NO8P/c1-6-8-10-12-14-16-18-20-21-23-24-26-28-30-32-34-41(44)48-38-40(39-50-52(46,47)49-37-36-43(3,4)5)51-42(45)35-33-31-29-27-25-22-19-17-15-13-11-9-7-2/h20-21,40H,6-19,22-39H2,1-5H3/b21-20-

[2-hexadecanoyloxy-3-[(Z)-octadec-9-enoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate

1-Oleoyl-2-palmitoyl lecithin; 1-Oleoyl-2-palmitoylphosphatidylcholine; ETC-588; Phosphatidyl choline (from egg yolk); 17118-56-8; [2-hexadecanoyloxy-3-[(Z)-octadec-9-enoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate; 8057-53-2; 8057-53-2 (from egg yolk);

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)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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