| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
Prostaglandin synthetase (PGS) (IC50 = 0.28 μM) [1]
5-Lipoxygenase (5-LO) (IC50 = 1.05 μM) [1] |
|---|---|
| ln Vitro |
The pure isomer of synthetic α-benzylidene-γ-butyrolactone is either trans or cis. It is the trans isomer, PGS-IN-1. Strong anti-inflammatory and PGS inhibitory properties are exhibited by PGS-IN-1 (IC50=0.28 μM). Additionally, PGS-IN-1 has strong inhibitory action on 5-lipoxygenase (IC50=1.05 μM)[1].
PGS-IN-1 inhibited microsomal prostaglandin synthetase with an IC50 value of 0.28 μM. [1] PGS-IN-1 inhibited cytosol 5-lipoxygenase activity with an IC50 value of 1.05 μM. [1] The compound showed potent inhibitory activity against both enzymes, whereas reference drug indomethacin had no 5-lipoxygenase inhibitory activity (IC50 > 100 μM). [1] |
| ln Vivo |
In the carrageenin-induced rat paw edema assay, PGS-IN-1 administered orally at 50 mg/kg produced 35% inhibition of edema formation. It was more potent than ibuprofen and phenylbutazone but less potent than indomethacin (which gave 33% inhibition at 5 mg/kg p.o.) in this model. [1]
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| Enzyme Assay |
Prostaglandin synthetase (PGS) assay: The test compound was dissolved in ethanol, with a final ethanol concentration of 2% in the assay. The reaction mixture (total volume 0.2 mL) contained 100 mM Tris-HCl buffer (pH 7.6), 4 mM glutathione, 4 mM epinephrine bitartrate, 20 μM [1-14C]arachidonic acid (0.05 μCi), microsomal enzyme (110 μg protein) from rabbit kidney medullas, and the test compound. The mixture was incubated for 15 minutes at 37°C with shaking. The reaction was stopped by adding 2.5 mL ethyl acetate and 25 μL of 1 N formic acid. The metabolites in the extract were separated by thin-layer chromatography, radioactive zones were located by radioautography, and the radioactivity was counted. PGS activity was measured in terms of both PGE2 and PGF2α production. [1]
5-Lipoxygenase assay: The cytosol fraction (600 μg protein per 0.2 mL per tube) from peritoneal polymorphonuclear leukocytes of male guinea pigs was used. The cytosol was preincubated with the test compound in the presence of 1 mM CaCl2 and 1 mM glutathione for 5 minutes at 30°C. Then the mixture was incubated with 20 μM [1-14C]arachidonic acid (0.1 μCi) for 5 minutes at 30°C with shaking. The reaction was terminated by adding 2.5 mL of chloroform-methanol (2:1) and 0.3 mL of 40 mM citric acid. The metabolites were separated by thin-layer chromatography, and 5-lipoxygenase activity was measured in terms of 5-hydroxyeicosatetraenoic acid (5-HETE) production. [1] |
| Animal Protocol |
Carrageenin-induced paw edema in rats: The test compound PGS-IN-1 was administered orally to groups of 4-6 male Wistar rats weighing 160-220 g. One hour after oral administration, 0.1 mL per rat of 1% carrageenin in 0.9% NaCl was injected subcutaneously into a hind paw. Paw volumes were measured 5 hours after the carrageenin injection. Edema inhibition was expressed as a percentage compared to the control group. [1]
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| References | |
| Additional Infomation |
PGS-IN-1 (KME-4, α-(3,5-di-tert-butyl-4-hydroxybenzylidene)-γ-butyrolactone) is a trans isomer, as determined by NMR spectroscopy (the olefinic proton shifted to lower field when the solvent was changed from CDCl3 to C6D6). It was synthesized via the Wittig reaction by condensing 3,5-di-tert-butyl-4-hydroxybenzaldehyde with α-triphenylphosphoranylidene-γ-butyrolactone in DMSO at 80°C for 20 hours, yielding 77.4% after recrystallization from ethanol. [1]
Structure-activity relationship analysis indicated that a tert-butyl group at the 3-position, an alkyl group at the 5-position, and an oxygen atom at the 4-position of the α-benzylidene-γ-butyrolactone ring system are necessary for antiinflammatory activity. PGS-IN-1 possesses this optimal substitution pattern. [1] |
| Molecular Formula |
C19H26O3
|
|---|---|
| Molecular Weight |
302.4079
|
| Exact Mass |
302.188
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| CAS # |
102271-49-8
|
| PubChem CID |
6438990
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| Appearance |
White to off-white solid powder
|
| LogP |
4.317
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
|
| Heavy Atom Count |
22
|
| Complexity |
426
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C1=CC(=CC(=C1O)C(C)(C)C)/C=C/2\CCOC2=O
|
| InChi Key |
DFPYHQJPGCODSB-UKTHLTGXSA-N
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| InChi Code |
InChI=1S/C19H26O3/c1-18(2,3)14-10-12(9-13-7-8-22-17(13)21)11-15(16(14)20)19(4,5)6/h9-11,20H,7-8H2,1-6H3/b13-9+
|
| Chemical Name |
(3E)-3-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]oxolan-2-one
|
| 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 | 3.3068 mL | 16.5338 mL | 33.0677 mL | |
| 5 mM | 0.6614 mL | 3.3068 mL | 6.6135 mL | |
| 10 mM | 0.3307 mL | 1.6534 mL | 3.3068 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.
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