| Size | Price | |
|---|---|---|
| 1mg | ||
| Other Sizes |
| Targets |
Thromboxane receptor; prostaglandin E2 synthase; PG/prostaglandin H2 analog; vasoconstrictor
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|---|---|
| ln Vitro |
Dose-response relationships for raised cytoplasmic free calcium concentration, [Ca2+]i, and shape change were measured simultaneously in quin2-loaded human platelets. With the calcium ionophore ionomycin the threshold [Ca2+]i for shape change was 300 nM with a maximal response at 800 nM. With 1 mM external Ca2+ the U44069 concentrations required to stimulate half-maximal shape change and an increase in [Ca2+]i were 2 and 41 nM, respectively. For PAF these values were 8.7 and 164 pg/ml, respectively. Low concentrations of U44069 and PAF evoked substantial shape change without any rise in [Ca2+]i. In the absence of external Ca2+, U44069 stimulated half-maximal shape change at 2 nM, and half-maximal elevation of [Ca2+]i at 69 nM: here, increased [Ca2+]i never reached the threshold [Ca2+]i for shape-change derived with ionomycin. These results suggest that some transduction mechanism other than elevated [Ca2+]i, as yet unidentified, can cause shape change [1].
|
| ln Vivo |
U-44069 is a stable prostaglandin (PG) H2 analogue and a potent vasoconstrictor. Its in vivo and in vitro actions mimic those of thromboxane A2. We have studied the effects of the calcium antagonist diltiazem upon the vasoconstriction induced by U-44069 using isolated rat aortic smooth muscle and isolated perfused rat kidney (IPRK). The administration of 10(-6)M U-44069 elicited maximally effective contractions in isolated aortic rings and increased 45Ca uptake from a control value of 285 +/- 6 mumol/kg to 344 +/- 8 mumol/kg. Diltiazem reduced U-44069-induced tension development and 45Ca uptake of isolated aortic smooth muscle 73 +/- 2 and 91 +/- 3%, respectively. The dose dependency of each of these effects of diltiazem was similar (EC50 = 369 nM and 334 nM for tension and 45Ca flux, respectively). When administered to the IPRK, 10(-6) M U-44069 caused a 82 +/- 3% decrease in glomerular filtration rate (GFR) and a 80 +/- 4% decrease in filtration fraction but reduced renal perfusate flow (RPF) only 13 +/- 8% (P less than 0.005). Diltiazem completely reversed the actions of U-44069 on the IPRK (EC50 = 288 nM and 323 nM for GFR and RPF, respectively). Diltiazem thus inhibited U-44069-induced tension development and 45Ca uptake by vascular smooth muscle and increased GFR within identical dose ranges. The contractile response of isolated rat glomeruli was also assessed. U-44069 reduced the volume of isolated glomeruli, but this action was neither prevented nor reversed by diltiazem. These results are consistent with the hypothesis that diltiazem increased GFR by inhibiting U-44069-induced Ca influx at preglomerular vessels. [2]
|
| Cell Assay |
Human platelet-rich plasma (PRP) was isolatedfrom freshly drawn blood and incubated with15 PM quin2 AM. 5 min before the end of the incubation 1OOpMaspirin and 40pg/ml apyrase were added to thePRP. The cells were resuspended in a Hepes-buffered physiological saline containing: 145 mMNaCl, 5 mM KCl, 1 mM MgS04, 10 mM Hepes,10 mM dextrose (pH 7.4) at 37°C. The cell suspen-sion also contained 0.05 U/ml hirudin and20 pg/ml apyrase. Before measurements weremade, aliquots of the cell suspension wereequilibrated to 37°C for several minutes and theexternal calcium concentration adjusted by adding1 mM CaCl2 or 1 mM NazHzEGTA as required.Quin2 fluorescence was monitored in a continuallystirred cell suspension, thermostatted to 37°C in aPerkin Elmer MPF 44A spectrofluorimeter. Theinstrument was adapted so that the absorbance ofthe stirred suspension could be monitored produc-ing a turbidometric trace like that produced in astandard aggregometer simultaneously withfluorescence. The quin2 fluorescence signalwas calibrated as described.
Calcium-selective electrodes were constructed byfusing Ca2+ -selective PVC matrix membranes on-to 1 mm PVC tubing with tetrahydrofuran. Thereference electrode consisted of a similar tubefilled with 3 M KC1 gelled in agar. The potentialdifference was measured by a specially constructedhigh independence electrometer and the electrode calibrated in a series of Ca2+ buffers containingfree Ca2+ in the range 10-7-10-3 M. Shape change was expressed as % maximaldeflection in absorbance recorded on the chartrecorder. Dose-response curves were fitted to thelogistic equation by computer using the ALLFITprogram [la]. The points are means f SE. Errorsquoted for EC50 values are approximate SE de-rived from this fitting procedure. |
| References |
|
| Additional Infomation |
Two recent reports have suggested thateither diacylglycerol or phosphatidylinositol4,5-bisphosphate may play a part in forming anucleation site for the polymerisation of actinwhich forms the microfilaments in pseudopodia.According to existing data [ 171there would be littlestimulation of inositol lipid turnover at the U44069concentrations which we find to cause shapechange without a measurable rise in [Ca’+]r. It isunclear whether this would be sufficient for theformation of nucleation sites. Changes in cyclicnucleotide levels or in cytoplasmic pH are unlikelyto be involved. CAMP and cGMP are inhibitors ofplatelet function, and cytoplasmic pHchanges less than 0.05 units following stimulation with U44069, assessed from the fluorescenceof trapped biscarboxyethylcarboxyfluorescein(Hallam, Simpson and Rink, unpublished). At pre-sent the nature of the putative alternative transduc-tion mechanism remains unclear. [1]
|
| Molecular Formula |
C21H34O4
|
|---|---|
| Molecular Weight |
350.49
|
| Exact Mass |
350.245
|
| Elemental Analysis |
C, 71.96; H, 9.78; O, 18.26
|
| CAS # |
56985-32-1
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| PubChem CID |
44364273
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
519.7±35.0 °C at 760 mmHg
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| Flash Point |
176.1±19.4 °C
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| Vapour Pressure |
0.0±3.1 mmHg at 25°C
|
| Index of Refraction |
1.548
|
| LogP |
3.88
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
25
|
| Complexity |
457
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
CCCCC[C@@H](/C=C/C1C2CC(C1C/C=C\CCCC(=O)O)OC2)O
|
| InChi Key |
DJKDIKIDYDXHDD-REGKDVDGSA-N
|
| InChi Code |
InChI=1S/C21H34O4/c1-2-3-6-9-17(22)12-13-18-16-14-20(25-15-16)19(18)10-7-4-5-8-11-21(23)24/h4,7,12-13,16-20,22H,2-3,5-6,8-11,14-15H2,1H3,(H,23,24)/b7-4-,13-12+/t16?,17-,18-,19+,20?/m0/s1
|
| Chemical Name |
(Z)-7-[(5S,6R)-5-[(E,3S)-3-hydroxyoct-1-enyl]-2-oxabicyclo[2.2.1]heptan-6-yl]hept-5-enoic acid
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| 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 | 2.8531 mL | 14.2657 mL | 28.5315 mL | |
| 5 mM | 0.5706 mL | 2.8531 mL | 5.7063 mL | |
| 10 mM | 0.2853 mL | 1.4266 mL | 2.8531 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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