| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
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| Targets |
Mineralocorticoid (MR)
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|---|---|
| ln Vitro |
MR antagonism causes apoptosis and accentuates GR-mediated apoptosis [1]
Blockade of MR with SPIRO (108–105M) resulted ina dose-dependent increase in levels of apoptosis(Figure 4a). The less-potent MR antagonist oxprenoate(RU28318)33–35only stimulated apoptosis when usedat 105M, the highest doses tested (Figure 4b). Theapoptotic actions of SPIRO and RU28318 mostprobably result from their counteraction of theprosurvival effects of the nanomolar (MR-activating)levels of corticosterone in the B27/Neurobasal med-ium; these results indicate that tonic occupation ofMR is essential for neuronal survival. The view thatMR activation promotes cell survival was boosted bythe finding that both MR antagonists synergized witha suboptimal dose of DEX (106M; 10-fold lower thanthe dose used in the previous experiment) to induceapoptosis; our observations show that manifestationof the full apoptotic potential of GR agonistsin vitrocan be masked by MR agonists that are inadvertentlypresent in the medium. [1] |
| Cell Assay |
Cells were exposed to drugs after 6 daysin vitro;exposure to experimental drugs was for 48 h. The GRagonist (DEX) was obtained as a sodium phosphatesalt in aqueous form and used at doses of either 106or 105M. The prototypic MR agonist aldosterone (ALDO) was used at a dose of 105M (survival studies) or 108M(translocation experiments) after solution in ethanol.Two MR antagonists were used alone or as cotreat-ments with DEX: spironolactone ([7a-(acetylthio)-3-oxo-17a-pregn-4-ene,21 carbolactone] (SPIRO); was used at between 109and 105M aftersolution in ethanol; oxprenoate potassium ((7a,17a)-17-Hydroxy-3-oxo-7-propylpregn-4-ene-21-carboxylicacid, potassium salt/RU28318), was used at doseranging from 109to 105M after direct solution ingrowing medium. Final ethanol concentrations in themedium were 0.01%; drug-naive cultures were incubated in Neurobasal/B27 medium containing0.01% ethanol for equivalent times. In all experi-ments, the position of wells subjected to control ordrug treatments was randomized; each experimentwas performed on at least three independent occa-sions.[1]
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| References | |
| Additional Infomation |
An important question arising from previous observations in vivo is whether glucocorticoids can directly influence neuronal survival in the hippocampus. To this end, a primary postnatal hippocampal culture system containing mature neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR) receptors was developed. Results show that the GR agonist dexamethasone (DEX) targets neurons (microtubule-associated protein 2-positive cells) for death through apoptosis. GR-mediated cell death was counteracted by the MR agonist aldosterone (ALDO). Antagonism of MR with spironolactone ([7alpha-(acetylthio)-3-oxo-17alpha-pregn-4-ene-21 carbolactone] (SPIRO)) causes a dose-dependent increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar levels of corticosterone present in the culture medium, which are sufficient to activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and another MR antagonist, oxprenoate potassium ((7alpha,17alpha)-17-hydroxy-3-oxo-7-propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX-induced apoptosis. These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR. [1]
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| Molecular Formula |
C25H37O4-.K+
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|---|---|
| Molecular Weight |
440.65718
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| Exact Mass |
440.233
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| Elemental Analysis |
C, 68.14; H, 8.46; K, 8.87; O, 14.52
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| CAS # |
76676-34-1
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| Related CAS # |
76676-34-1 (potassium);786592-95-8 (free acid);
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| PubChem CID |
23677972
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| Appearance |
White to off-white solid powder
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| Boiling Point |
569.3ºC at 760 mmHg
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| Flash Point |
312.2ºC
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| LogP |
3.805
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
733
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CCC[C@@H]1CC2=CC(=O)CC[C@@]2([C@@H]3[C@@H]1[C@@H]4CC[C@]([C@]4(CC3)C)(CCC(=O)[O-])O)C.[K+]
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| InChi Key |
HXJITUGMCJCKCE-UYOQDFFISA-M
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| InChi Code |
InChI=1S/C25H38O4.K/c1-4-5-16-14-17-15-18(26)6-10-23(17,2)19-7-11-24(3)20(22(16)19)8-12-25(24,29)13-9-21(27)28;/h15-16,19-20,22,29H,4-14H2,1-3H3,(H,27,28);/q;+1/p-1/t16-,19+,20+,22-,23+,24+,25-;/m1./s1
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| Chemical Name |
potassium;3-[(7R,8R,9S,10R,13S,14S,17R)-17-hydroxy-10,13-dimethyl-3-oxo-7-propyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl]propanoate
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| Synonyms |
Oxprenoate potassium; 76676-34-1; RU 28318, potassium salt; Oxprenoas kalii; Oxprenoate potassium [INN]; Oxprenoas kalii [Latin]; Oxprenoato potasico; Oxprenoato potasico [Spanish];
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 2.2693 mL | 11.3466 mL | 22.6932 mL | |
| 5 mM | 0.4539 mL | 2.2693 mL | 4.5386 mL | |
| 10 mM | 0.2269 mL | 1.1347 mL | 2.2693 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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