Esaxerenone |
| Catalog No.GC19143 |
Esaxerenone (CS-3150), a selective nonsteroidal mineralocorticoid receptor antagonist, has been shown to bind to mineralocorticoid receptors, thereby inhibiting aldosterone binding and activation of the receptor.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1632006-28-0
Sample solution is provided at 25 µL, 10mM.
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Esaxerenone (CS-3150), a selective nonsteroidal mineralocorticoid receptor antagonist, has been shown to bind to mineralocorticoid receptors, thereby inhibiting aldosterone binding and activation of the receptor [1]. Esaxerenone inhibited 3H-aldosterone binding to mineralocorticoid receptor in a concentration-dependent manner with IC50 of 9.4 nM. Esaxerenone inhibited aldosterone-induced human mineralocorticoid receptor activation in a concentration-dependent manner with IC50 of 3.7 nM. Esaxerenone showed antagonist activity for rat mineralocorticoid receptor with IC50 of 4.9 nM [1].
Esaxerenone (10,100nM) reversed the reduction in insulin-induced Akt phosphorylation caused by aldosterone in insulin target cells, such as adipocytes, hepatocytes, and myocytes. Pretreatment with esaxerenone significantly ameliorated insulin signaling in these cell types [2].
Esaxerenone (3 mg/kg) significantly inhibited DOCA/salt-loading induced elevation in systolic blood pressure compared with the control rats (DOCA-untreated) [1]. Esaxerenone (0.25-2 mg/kg) was orally administered once a day to DS rats fed a high salt diet for 7 weeks. The high salt diet significantly increased systolic blood pressure, which was prevented by treatment with Esaxerenone in a dose-dependent manner with no hyperkalemia (>5.5 mEq/L). Esaxerenone also suppressed proteinuria and renal hypertrophy induced by the high salt diet. Histopathological examination of kidneys showed that CS-3150 markedly ameliorated glomerulosclerosis, tubular injury and tubulointerstitial fibrosis. CS-3150 inhibited left ventricular hypertrophy and elevation of plasma brain natriuretic peptide level [3]. In preclinical models, the pharmacokinetic profile of esaxerenone is the basis for a long-lasting action (plasma half-life rats: 6.5-6.9 h), high oral bioavailability and predominant excretion via faeces [1,4]. A long plasma half-life of esaxerenone has been confirmed in healthy human volunteers (plasma half-life: 30 h) [5].
References:
[1]. Arai K, Homma T, Morikawa Y, et al. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist[J]. European Journal of Pharmacology, 2015, 761: 226-234.
[2]. Bavuu O, Fukuda D, Ganbaatar B, et al. Esaxerenone, a selective mineralocorticoid receptor blocker, improves insulin sensitivity in mice consuming high-fat diet[J]. European Journal of Pharmacology, 2022, 931: 175190.
[3]. Arai K, Tsuruoka H, Homma T. CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist, prevents hypertension and cardiorenal injury in Dahl salt-sensitive hypertensive rats[J]. European journal of pharmacology, 2015, 769: 266-273.
[4]. Wan N, Rahman A, Nishiyama A. Esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker (MRB) in hypertension and chronic kidney disease[J]. Journal of Human Hypertension. 2021 Feb;35(2):148-56.
[5]. Yamada, M., Mendell, J., Takakusa, H., Shimizu, T., & Ando, O. (2019). Pharmacokinetics, metabolism, and excretion of [14C] esaxerenone, a novel mineralocorticoid receptor blocker in humans[J]. Drug Metabolism and Disposition, 47(3), 340-349. Diseases, 2013, 72(Suppl 3): A129-A129.
| Cell experiment [1]: | |
Cell lines | 3T3-L1 preadipocytes, The human hepatoma cell line HepG2, Differentiated C2C12 myotubes |
Preparation Method | The cells were starved in DMEM containing 0.1% charcoal/dextran-treated FBS for 24 h, before stimulation with aldosterone. Cells were pretreated with 10 or 100 nM esaxerenone for 8 h before aldosterone treatment. The effects of aldosterone on insulin signaling were examined in cells treated with 100 or 1000 nM aldosterone for 4 h. Insulin signaling in these cell types was examined after stimulation with 17 nM insulin for 15 min. |
Reaction Conditions | 10 or 100 nM for 8 hours |
Applications | Aldosterone significantly abrogated insulin signaling, as determined by insulin-induced Akt phosphorylation in insulin target cells, 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes, in a dose-dependent manner. Pretreatment with esaxerenone significantly ameliorated insulin signaling in these cell types. |
| Animal experiment [2]: | |
Animal models | Male Sprague-Dawley (SD) rats |
Preparation Method | Esaxerenone (0.3, 1 and 3 mg/kg), dissolved in N,N-dimethylacetamide (DMA):Tween 80:saline solution in a ratio of 1:1:8 (v/v/v), was orally administered to eight-week-old male SD rats. Blood samples were collected from the cervical vein at 0.25, 0.5, 1, 2, 4, 6, 8, 24 and 48 h after administration, and drug concentrations in plasma were measured by liquid chromatography-tandem mass spectrometry and API3000. |
Dosage form | 0.3, 1 and 3 mg/kg, oral |
Applications | Single oral administration of Esaxerenone at 0.3, 1 and 3 mg/kg, the tmax was 2.0-4.5 h and t1/2 was 6.5-6.9 h. The Cmax and area under the curve to infinity (AUC0-inf) were dose-dependently increased. |
References: | |
| Cas No. | 1632006-28-0 | SDF | |
| Canonical SMILES | O=C(C1=CN(CCO)C(C2=CC=CC=C2C(F)(F)F)=C1C)NC3=CC=C(S(=O)(C)=O)C=C3 | ||
| Formula | C22H21F3N2O4S | M.Wt | 466.47 |
| Solubility | DMSO : ≥ 125 mg/mL (267.97 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1438 mL | 10.7188 mL | 21.4376 mL |
| 5 mM | 0.4288 mL | 2.1438 mL | 4.2875 mL |
| 10 mM | 0.2144 mL | 1.0719 mL | 2.1438 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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