| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Esaxerenone selectively binds to the mineralocorticoid receptor (MR) and inhibits aldosterone binding and activation of the receptor. It inhibits ³H-aldosterone binding to the mineralocorticoid receptor with an IC₅₀ value of 9.4 nM. As a silent antagonist, esaxerenone blocks aldosterone-induced transcriptional activation of human MR without activating the receptor itself.
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| ln Vitro |
In vitro, esaxerenone binds to the mineralocorticoid receptor and inhibits ³H-aldosterone binding with an IC₅₀ of 9.4 nM. It is a highly selective non-steroidal MR antagonist. The compound's selectivity for MR over other steroid hormone receptors has been characterized in receptor binding and functional assays. Esaxerenone inhibits aldosterone-induced transcriptional activation of human MR.
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| ln Vivo |
The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increased with increasing dose after a single oral administration of 0.1, 0.3, 1, and 3 mg/kg esaxerenone. Esaxerenone's maximum plasma concentration (Tmax) can be reached in 2.0–4.5 hours. The systemic clearance (CL) and volume of distribution (Vss) at steady state following an intravenous injection of 0.1, 0.3, 1 and 3 mg/kg of esaxerenone were 3.53 to 6.69 mL/min/kg and 1.47 to 2.49 L/kg, respectively. Rats: 2.79 to 3.69 mL/min/kg; cynomolgus monkeys: 1.34 to 1.54 L/kg; and rats: 2.79 to 3.69 mL/min/kg. Rat urine and feces excreted 3.9% and 91.4%, respectively, of the dosed radioactive material within 168 hours of administration, for a total of 95.2%. In monkeys, 82.3% of the radioactive material expelled in feces and 11.5% in urine made up a total of 93.9% within 168 hours [1].
In vivo, esaxerenone has been shown to have antihypertensive effects in animal models. After administration at doses of 0.1, 0.3, 1, and 3 mg/kg, the compound reduces blood pressure. It is being developed for the treatment of hypertension, essential hypertension, hyperaldosteronism, and diabetic nephropathies. Clinical trials are ongoing to evaluate its efficacy and safety in these indications. |
| Enzyme Assay |
Non-cellular receptor binding assays for esaxerenone involve competitive radioligand binding displacement studies using mineralocorticoid receptor preparations. The receptor is incubated with [³H]-aldosterone and varying concentrations of esaxerenone. Following incubation and filtration, bound radioactivity is measured by scintillation counting. IC₅₀ values are determined from displacement curves and converted to Ki values using the Cheng-Prusoff equation.
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| Cell Assay |
In vitro cellular assays for esaxerenone involve treating cells expressing the mineralocorticoid receptor with the compound and measuring receptor-mediated transcriptional activity. Reporter gene assays using mineralocorticoid response element (MRE)-luciferase constructs are commonly used. Cells are treated with aldosterone in the presence of varying concentrations of esaxerenone, and luciferase activity is measured to quantify the inhibition of aldosterone-induced transcriptional activation.
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| Animal Protocol |
In vivo animal experiments with esaxerenone are conducted in rodent models of hypertension. Rats are treated with esaxerenone via oral administration at doses of 0.1, 0.3, 1, and 3 mg/kg. Blood pressure is measured using tail-cuff or telemetry methods. The compound's effects on electrolyte balance, renal function, and markers of mineralocorticoid receptor activity are also assessed. Pharmacokinetic studies characterize absorption and distribution.
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| ADME/Pharmacokinetics |
Esaxerenone has a molecular weight of 399.46 and a molecular formula of C₂₂H₂₂FN₃O₃S. It is a solid powder with a purity of ≥98%. The compound is soluble in DMSO and other organic solvents. It is typically stored at -20°C, protected from light and moisture. The compound is stable under recommended storage conditions.
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| Toxicity/Toxicokinetics |
Esaxerenone is generally well-tolerated at therapeutic doses. Common side effects may include hyperkalemia, hypotension, and renal impairment. As a mineralocorticoid receptor antagonist, it should be used with caution in patients with renal impairment or hyperkalemia. Standard safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
Esaxerenone is being investigated in the clinical trial NCT02722265 (a long-term study of CS-3150 as monotherapy or in combination with other antihypertensive drugs in Japanese patients with essential hypertension).
Esaxerenone (CS-3150; XL-550; CAS 1632006-28-0) is a non-steroidal, highly selective mineralocorticoid receptor antagonist with an IC₅₀ of 9.4 nM for inhibiting ³H-aldosterone binding. It is marketed as Minnebro and is being developed for the treatment of hypertension, hyperaldosteronism, and diabetic nephropathies. The compound is available from various commercial suppliers for research applications. |
| Molecular Formula |
C22H21F3N2O4S
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|---|---|
| Molecular Weight |
466.4752
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| Exact Mass |
466.117
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| CAS # |
1632006-28-0
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| Related CAS # |
1632006-28-0;880780-76-7;1072195-82-4 (+ isomer);1072195-83-5 (- isomer);
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| PubChem CID |
25052023
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| Appearance |
White to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
581.3±50.0 °C at 760 mmHg
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| Flash Point |
305.4±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.581
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| LogP |
3.15
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
747
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NOSNHVJANRODGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21F3N2O4S/c1-14-18(21(29)26-15-7-9-16(10-8-15)32(2,30)31)13-27(11-12-28)20(14)17-5-3-4-6-19(17)22(23,24)25/h3-10,13,28H,11-12H2,1-2H3,(H,26,29)
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| Chemical Name |
1-(2-hydroxyethyl)-4-methyl-N-(4-(methylsulfonyl)phenyl)-5-(2-(trifluoromethyl)phenyl)-1H-pyrrole-3-carboxamide
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| Synonyms |
Esaxerenone CS-3150 CS 3150 CS3150 XL-550 XL550 XL 550.
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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) |
DMSO : ~100 mg/mL (~214.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.08 mg/mL (4.46 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1437 mL | 10.7186 mL | 21.4371 mL | |
| 5 mM | 0.4287 mL | 2.1437 mL | 4.2874 mL | |
| 10 mM | 0.2144 mL | 1.0719 mL | 2.1437 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.
Comparative clinical trial of Esaxerenone for hypertension with moderate chronic kidney disease
CTID: UMIN000037124
Phase: Status: Complete: follow-up complete
Date: 2019-06-20
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