| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Na+/K+-ATPase (sodium/potassium adenosine triphosphatase) and SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATPase 2). Istaroxime inhibits Na+/K+-ATPase (IC50 = 0.11 μM) and activates SERCA2. Inhibition of Na+/K+-ATPase increases intracellular sodium, which reverses the sodium/calcium exchanger driving force, inhibiting calcium extrusion and facilitating calcium entry.
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| ln Vitro |
Na+, K+-ATPase is regulated by isostaroxime hydrochronous, a positive inotropic substance. With an IC50 value of 0.43±0.15 μM, istaxime hydrochloride (PST2744) modifies the Na+/K+-ATPase activity in pH solution[2]. Microorganisms with Na+/K+-ATPase activity had an efficacious concentration of 8.5 μM for PST2744 [3].
Istaroxime inhibits Na+/K+-ATPase with an IC50 of 0.11 μM. It increases intracellular calcium by improving the efficacy by which intracellular calcium triggers sarcoplasmic reticulum calcium release, and by accelerating the inactivation state of L-type calcium channels, which allow for calcium influx. The compound demonstrates positive inotropic effects in cardiac tissue preparations. |
| ln Vivo |
Istaxime hydrochloride (PST2744) generates a steady increase in +dP/dtmax during the infusion, reaching 80% (ED80) at a dose (EDmax) of 4.88 ± 0.6 mg/kg and 80% (ED80) at a dose (EDmax) of 4.88 ± 0.6 mg/kg. At 0.6 mg/kg, the maximum is 140±3.5%[3].
In vivo assays prove Istaroxime is consistently safer than digoxin. It increases intracellular calcium by improving the efficacy of intracellular calcium triggering sarcoplasmic reticulum calcium release. Istaroxime has been evaluated in animal models of heart failure and shows improved hemodynamic parameters compared to standard therapies. Detailed in vivo efficacy data has been reported in preclinical studies. |
| Enzyme Assay |
Na+/K+-ATPase enzyme activity assay: Purified Na+/K+-ATPase is incubated with varying concentrations of Istaroxime and ATP in assay buffer containing NaCl, KCl, MgCl₂, and Tris-HCl pH 7.4 at 37°C for 30 min. The inorganic phosphate released is measured by colorimetric detection. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Sarcoplasmic reticulum calcium uptake assay: Cardiac SR vesicles are incubated with Istaroxime at varying concentrations and ⁴⁵Ca²⁺ in assay buffer containing ATP, oxalate, and MgCl₂ at 37°C for 10-30 min. Vesicles are filtered, and radioactivity is measured by scintillation counting. SERCA2 activation is assessed by increased calcium uptake rates.
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| Animal Protocol |
Heart failure animal model: Rats or dogs with induced heart failure are administered Istaroxime via intravenous infusion at various doses. Hemodynamic parameters including cardiac output, left ventricular pressure, and heart rate are measured. Safety profile is compared to digoxin treatment groups. Endpoints include survival, functional recovery, and biomarker analysis.
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| ADME/Pharmacokinetics |
Istaroxime has a molecular weight of 396.95 g/mol and molecular formula C₂₁H₃₃ClN₂O₃. It is administered intravenously. Detailed pharmacokinetic parameters including half-life, Cmax, AUC, and clearance have been characterized in preclinical and clinical studies. The compound shows favorable PK properties for acute heart failure indications.
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| Toxicity/Toxicokinetics |
Toxicity has been evaluated in preclinical studies. In vivo assays prove Istaroxime is consistently safer than digoxin. The compound shows an improved safety profile compared to cardiac glycosides, with a wider therapeutic window. Detailed toxicity data including NOAEL and organ-specific effects have been reported in preclinical safety studies.
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| References |
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| Additional Infomation |
Istaroxime is a first-in-class positive inotropic agent with a dual mechanism: Na+/K+-ATPase inhibition (IC50 = 0.11 μM) and SERCA2 activation. It has been investigated in clinical trials for acute heart failure. The compound represents a novel approach to improving cardiac contractility without the arrhythmogenic risks associated with traditional inotropes. No approved上市 status has been reported.
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| Molecular Formula |
C21H33CLN2O3
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|---|---|
| Molecular Weight |
396.956
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| Exact Mass |
396.218
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| CAS # |
374559-48-5
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| Related CAS # |
Istaroxime;203737-93-3
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| PubChem CID |
72941813
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| Appearance |
White to light brown solid powder
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| LogP |
4.61
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
645
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| Defined Atom Stereocenter Count |
6
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| SMILES |
C[C@]12CCC(=NOCCN)C[C@@H]1C(=O)C[C@@H]3[C@@H]2CC[C@]4([C@H]3CCC4=O)C.Cl
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| InChi Key |
AXHJYJDJXNOGNI-DESZRGPQSA-N
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| InChi Code |
InChI=1S/C21H32N2O3.ClH/c1-20-7-5-13(23-26-10-9-22)11-17(20)18(24)12-14-15-3-4-19(25)21(15,2)8-6-16(14)20;/h14-17H,3-12,22H2,1-2H3;1H/t14-,15-,16-,17+,20+,21-;/m0./s1
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| Chemical Name |
(5S,8R,9S,10R,13S,14S)-3-(2-aminoethoxyimino)-10,13-dimethyl-1,2,4,5,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-6,17-dione;hydrochloride
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| Synonyms |
PST2744 HCl; Istaroxime
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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) |
DMSO : ≥ 45 mg/mL (~113.36 mM)
H2O : ~25 mg/mL (~62.98 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.30 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 25.0 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: ≥ 2.5 mg/mL (6.30 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 12.5 mg/mL (31.49 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5191 mL | 12.5957 mL | 25.1915 mL | |
| 5 mM | 0.5038 mL | 2.5191 mL | 5.0383 mL | |
| 10 mM | 0.2519 mL | 1.2596 mL | 2.5191 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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