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Istaroxime, formerly known as PST-2744, is a novel and potent positive inotropic agent and an inhibitor of Na+,K+-ATPase with IC50 of 0.11 μM.It mediates its action through inhibition of sodium/potassium adenosine triphosphatase (Na+/K+ ATPase). Na+/K+ ATPase inhibition increases intracellular sodium levels, which reverses the driving force of the sodium/calcium exchanger, inhibiting calcium extrusion and possibly facilitating calcium entry. Additionally, Istaroxime 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.
Physicochemical Properties
| Molecular Formula | C21H32N2O3 |
| Molecular Weight | 360.490386009216 |
| Exact Mass | 360.241 |
| CAS # | 203737-93-3 |
| Related CAS # | Istaroxime hydrochloride;374559-48-5 |
| PubChem CID | 9841834 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 511.1±60.0 °C at 760 mmHg |
| Flash Point | 262.9±32.9 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.651 |
| LogP | 1.89 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 26 |
| Complexity | 645 |
| Defined Atom Stereocenter Count | 6 |
| SMILES | O=C1CC[C@@]2([H])[C@]3([H])CC([C@@]4([H])C/C(CC[C@]4(C)[C@@]3([H])CC[C@@]21C)=N/OCCN)=O |
| InChi Key | MPYLDWFDPHRTEG-PAAYLBSLSA-N |
| InChi Code | InChI=1S/C21H32N2O3/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/b23-13+/t14-,15-,16-,17+,20+,21-/m0/s1 |
| Chemical Name | (3E,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 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | Istaroxime inhibits Na+,K+-ATPase, which functions as a positive inotropic chemical [2]. With an IC50 value of 0.43 ± 0.15 μM, isostaroxime (PST2744) inhibits the activity of Na+/K+-ATPase in the kidney of a dog. PST2744 potency was found to be 8.5 μM in guinea pig kidney preparations when Na+/K+-ATPase activity was inhibited [3]. |
| ln Vivo | Istaroxime (PST2744) generates a steady increase in +dP/dtmax during the infusion, reaching 80% (ED80) at a cumulative dose of 1.89±0.37 mg/kg and peaking at 140±3.5% at a cumulative dose (EDmax) of 4.88 ±0.6 mg/kg[3]. |
| References |
[1]. Novel analogues of istaroxime, a potent inhibitor of Na+,K+-ATPase: synthesis and structure-activity relationship. J Med Chem. 2008 Aug 14;51(15):4601-8. [2]. Novel analogues of Istaroxime, a potent inhibitor of Na(+),K(+)-ATPase: Synthesis, structure-activity relationship and 3D-quantitative structure-activity relationship of derivatives at position 6 on the androstane scaffold. Bioorg Med Ch. [3]. Pharmacological profile of the novel inotropic agent (E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744). J Pharmacol Exp Ther. 2002 Nov;303(2):592-600. |
| Additional Infomation |
Drug Indication Investigated for use/treatment in heart disease. Mechanism of Action Reduces the sodium-potassium adenosine triphosphatase (ATPase) activity and stimulates the sarcoplasmic calcium ATPase isoform 2 reuptake function. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7740 mL | 13.8700 mL | 27.7400 mL | |
| 5 mM | 0.5548 mL | 2.7740 mL | 5.5480 mL | |
| 10 mM | 0.2774 mL | 1.3870 mL | 2.7740 mL |