IP; Prodrug of PGI2; Vasodilator

The number of blood vessels created increased significantly after treatment with beraprost sodium (0.1, 1.0, and 10.0 μM; 24 hours), and BPS is crucial for angiogenic activity [1]. When endothelial cells were treated with beraprost sodium (0.1, 1.0, and 10.0 μM) for 24 hours, the amount of VE-cadherin in the cell-cell contact area increased, and their shape tended to be normal in contrast to cells grown in hypoxic environments [1].

Beraprost sodium is an oral medication that is administered once day for three to seven days at a dose of 0.6 mg/kg. It has the ability to lower renal oxidative stress and further prevent renal interstitial fibrosis. fibrosis [1].

Tube formation assay[1] In brief, endothelial cells (1 × 104) were seeded in a 48-well plate coated with 100 μl of growth factor-reduced Matrigel TM and incubated with and without varied concentrations of BPS (Beraprost sodium) at 0.1, 1.0, and 10.0 μmol/l for tube stabilization for 24 h at 37 °C. Tube formation was quantified by measuring the total tube loops in five random microscopic fields with a computer-assisted microscope

The HUVECs were cultured in a modified minimum essential medium supplemented with 10% fetal bovine serum and 1% mycillin at 37 °C in 5% CO2 and 95% air. HUVECs in hypoxia group were cultured for 12 h into an airtight humidified chamber flushed with a gas mixture containing 5% CO2, 95% N2, and 1% O2 at 37 °C. HUVECs in hypoxia + BPS group were cultured with BPS (Beraprost sodium) at 1.0 μmol/l. The cells were cultured according to the manufacturer’s instructions and the culture medium was changed every 2 or 3 days. HUVECs at passage 3 were used for the following experiments[1].

[1]. Li S, et al. Beraprost sodium mitigates renal interstitial fibrosis through repairing renal microvessels.J Mol Med (Berl). 2019 Jun;97(6):777-791.

Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.

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Pharmacodynamics
Beraprost is a stable, orally active prostacyclin analogue with vasodilatory, antiplatelet and cytoprotective effects. Beraprost is generally well tolerated and appears to be an effective agent in the treatment of patients with Buerger's disease and arteriosclerosis obliterans. Comparative data from a large randomised trial indicated that the drug appears as effective as ticlopidine in patients with these conditions. In patients with intermittent claudication, significant benefits of beraprost compared with placebo were reported in a randomised clinical trial; however, the use of beraprost in these patients is not supported by recent preliminary unpublished data from a large, phase III, placebo-controlled study. Limited data suggest some efficacy with long-term beraprost treatment of patients with PAH, where options are few and where oral administration of the drug could be a considerable advantage over intravenous prostacyclin (PGI2) therapy.

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Absorption
Oral bioavailability is 50–70%.
Biological Half-Life
35–40 minutes

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Mechanism of Action
Beraprost acts by binding to prostacyclin membrane receptors ultimately inhibiting the release of Ca2+ from intracellular storage sites. This reduction in the influx of Ca2+ has been postulated to cause relaxation of the smooth muscle cells and vasodilation.

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Pharmacodynamics
Beraprost is a stable, orally active prostacyclin analogue with vasodilatory, antiplatelet and cytoprotective effects. Beraprost is generally well tolerated and appears to be an effective agent in the treatment of patients with Buerger's disease and arteriosclerosis obliterans. Comparative data from a large randomised trial indicated that the drug appears as effective as ticlopidine in patients with these conditions. In patients with intermittent claudication, significant benefits of beraprost compared with placebo were reported in a randomised clinical trial; however, the use of beraprost in these patients is not supported by recent preliminary unpublished data from a large, phase III, placebo-controlled study. Limited data suggest some efficacy with long-term beraprost treatment of patients with PAH, where options are few and where oral administration of the drug could be a considerable advantage over intravenous prostacyclin (PGI2) therapy.

C24H30O5

398.499

398.209

88430-50-6

88430-50-6 (free acid);88475-69-8 (sodium);

5282428

Typically exists as solid at room temperature

1.3±0.1 g/cm3

572.1±50.0 °C at 760 mmHg

193.1±23.6 °C

0.0±1.7 mmHg at 25°C

1.625

2.87

CC#CCC(C)C(/C=C\C1C(CC2C1C3=CC=CC(=C3O2)CCCC(=O)O)O)O

CTPOHARTNNSRSR-OUKQBFOZSA-N

InChI=1S/C24H30O5/c1-3-4-7-15(2)19(25)13-12-17-20(26)14-21-23(17)18-10-5-8-16(24(18)29-21)9-6-11-22(27)28/h5,8,10,12-13,15,17,19-21,23,25-26H,6-7,9,11,14H2,1-2H3,(H,27,28)/b13-12+

4-[2-hydroxy-1-[(E)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoic acid

ML-1229; MDL-201229; beraprost; 88430-50-6; 88430-50-6 (free acid); 4-[2-hydroxy-1-[(E)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoic acid; Beraprost (USAN); 1H-Cyclopenta(b)benzofuran-5-butanoic acid, 2,3,3a,8b-tetrahydro-2-hydroxy-1-(3-hydroxy-4-methyl-1-octen-6-ynyl)-; 4-(2-Hydroxy-1-(3-hydroxy-4-methyloct-1-en-6-yn-1-yl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl)butanoic acid; 4-(1,2,3a,8b-tetrahydro-2-hydroxy-1-(3-hydroxy-4-methyloct-6-yne-1-enyl)-5-cyclopenta(b)benzofuranyl)butyrate; MDL 201229

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.)