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MedKoo Cat#: 563726 | Name: Istaroxime HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Istaroxime, also known as PST-2744, is a positive inotropic agent that 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.

Chemical Structure

Istaroxime HCl
Istaroxime HCl
CAS#374559-48-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 563726

Name: Istaroxime HCl

CAS#: 374559-48-5 (HCl)

Chemical Formula: C21H33ClN2O3

Exact Mass:

Molecular Weight: 396.96

Elemental Analysis: C, 63.54; H, 8.38; Cl, 8.93; N, 7.06; O, 12.09

Price and Availability

Size Price Availability Quantity
5mg USD 450.00 2 weeks
10mg USD 850.00 2 weeks
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Related CAS #
203737-93-3 (free base) 203738-46-9 (E-isomer) 1046809-08-8 (Z-isomer) 374559-48-5 (HCl) 203737-94-4 (oxalate)
Synonym
Istaroxime HCl; PST2744; PST 2744; PST-2744; PST-2744 HCl; PST-2744 hydrochloride
IUPAC/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 Hydrochloride
InChi Key
AXHJYJDJXNOGNI-ROJIRLEOSA-N
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/b23-13+;/t14-,15-,16-,17+,20+,21-;/m0./s1
SMILES Code
O=C(C[C@@]1([H])[C@]2([H])CC3)[C@@]4([H])C/C(CC[C@]4(C)[C@@]1([H])CC[C@]2(C)C3=O)=N/OCCN.[H]Cl
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Istaroxime hydrochloride is a Na+/K+-ATPase inhibitor (IC50=0.11 μM) and a sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA 2) activator.
In vitro activity:
As shown in Figure 1A, treatment of the DU-145 prostate cancer cells with 5µM istaroxime significantly inhibited cell motility, manifested by the diminished wound width as compared to control untreated cells (Fig. 1B). This finding was fully supported by the transwell assay, showing potent inhibition of 24 h cell migration potential, even at lower istaroxime concentrations (Fig. 1C). Reference: Cell Physiol Biochem. 2017;42(4):1366-1376. https://pubmed.ncbi.nlm.nih.gov/28704809/
In vivo activity:
To this end, cardiomyocytes of adult wild type and plna R14del zebrafish hearts were measured at 1 and 4 Hz before and after treatment with istaroxime. Interestingly, istaroxime treatment resulted in a significant shortening of APD20, APD50, and APD90 and a complete absence of APD alternans (Fig. 7A–D). The effects of istaroxime on APD were confirmed in vivo, using high-speed fluorescence imaging on embryos expressing VSFP Butterfly-CY (Fig. S12C). Reference: Nat Commun. 2021 Dec 9;12(1):7151. https://pubmed.ncbi.nlm.nih.gov/34887420/
Solvent mg/mL mM
Solubility
DMSO 45.0 113.36
Water 25.0 62.98
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 396.96 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Stagno MJ, Zacharopoulou N, Bochem J, Tsapara A, Pelzl L, Al-Maghout T, Kallergi G, Alkahtani S, Alevizopoulos K, Dimas K, Calogeropoulou T, Warmann SW, Lang F, Schmid E, Stournaras C. Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells. Cell Physiol Biochem. 2017;42(4):1366-1376. doi: 10.1159/000479200. Epub 2017 Jul 14. PMID: 28704809. 2. Wallner M, Khafaga M, Kolesnik E, Vafiadis A, Schwantzer G, Eaton DM, Curcic P, Köstenberger M, Knez I, Rainer PP, Pichler M, Pieske B, Lewinski DV. Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial functional effects in healthy and diseased human myocardium. Oncotarget. 2017 Jul 25;8(30):49264-49274. doi: 10.18632/oncotarget.17540. PMID: 28514771; PMCID: PMC5564766. 3. Kamel SM, van Opbergen CJM, Koopman CD, Verkerk AO, Boukens BJD, de Jonge B, Onderwater YL, van Alebeek E, Chocron S, Polidoro Pontalti C, Weuring WJ, Vos MA, de Boer TP, van Veen TAB, Bakkers J. Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy. Nat Commun. 2021 Dec 9;12(1):7151. doi: 10.1038/s41467-021-27461-8. PMID: 34887420; PMCID: PMC8660846. 4. Torre E, Arici M, Lodrini AM, Ferrandi M, Barassi P, Hsu SC, Chang GJ, Boz E, Sala E, Vagni S, Altomare C, Mostacciuolo G, Bussadori C, Ferrari P, Bianchi G, Rocchetti M. SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy. Cardiovasc Res. 2022 Mar 16;118(4):1020-1032. doi: 10.1093/cvr/cvab123. PMID: 33792692; PMCID: PMC8930067.
In vitro protocol:
1. Stagno MJ, Zacharopoulou N, Bochem J, Tsapara A, Pelzl L, Al-Maghout T, Kallergi G, Alkahtani S, Alevizopoulos K, Dimas K, Calogeropoulou T, Warmann SW, Lang F, Schmid E, Stournaras C. Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells. Cell Physiol Biochem. 2017;42(4):1366-1376. doi: 10.1159/000479200. Epub 2017 Jul 14. PMID: 28704809. 2. Wallner M, Khafaga M, Kolesnik E, Vafiadis A, Schwantzer G, Eaton DM, Curcic P, Köstenberger M, Knez I, Rainer PP, Pichler M, Pieske B, Lewinski DV. Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial functional effects in healthy and diseased human myocardium. Oncotarget. 2017 Jul 25;8(30):49264-49274. doi: 10.18632/oncotarget.17540. PMID: 28514771; PMCID: PMC5564766.
In vivo protocol:
1. Kamel SM, van Opbergen CJM, Koopman CD, Verkerk AO, Boukens BJD, de Jonge B, Onderwater YL, van Alebeek E, Chocron S, Polidoro Pontalti C, Weuring WJ, Vos MA, de Boer TP, van Veen TAB, Bakkers J. Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy. Nat Commun. 2021 Dec 9;12(1):7151. doi: 10.1038/s41467-021-27461-8. PMID: 34887420; PMCID: PMC8660846. 2. Torre E, Arici M, Lodrini AM, Ferrandi M, Barassi P, Hsu SC, Chang GJ, Boz E, Sala E, Vagni S, Altomare C, Mostacciuolo G, Bussadori C, Ferrari P, Bianchi G, Rocchetti M. SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy. Cardiovasc Res. 2022 Mar 16;118(4):1020-1032. doi: 10.1093/cvr/cvab123. PMID: 33792692; PMCID: PMC8930067.
1: Carubelli V, Zhang Y, Metra M, Lombardi C, Felker GM, Filippatos G, O'Connor CM, Teerlink JR, Simmons P, Segal R, Malfatto G, La Rovere MT, Li D, Han X, Yuan Z, Yao Y, Li B, Lau LF, Bianchi G, Zhang J; Istaroxime ADHF Trial Group. Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. Eur J Heart Fail. 2020 Jan 23. doi: 10.1002/ejhf.1743. [Epub ahead of print] PubMed PMID: 31975496. 2: Buttà C, Tuttolomondo A, Petrantoni R, Miceli G, Pinto A. Old And New Drugs For Treatment Of Advanced Heart Failure. Curr Pharm Des. 2019 Dec 26. doi: 10.2174/1381612826666191226165402. [Epub ahead of print] PubMed PMID: 31878852. 3: Kislitsina ON, Rich JD, Wilcox JE, Pham DT, Churyla A, Vorovich EB, Ghafourian K, Yancy CW. Shock - Classification and Pathophysiological Principles of Therapeutics. Curr Cardiol Rev. 2019;15(2):102-113. doi: 10.2174/1573403X15666181212125024. Review. PubMed PMID: 30543176; PubMed Central PMCID: PMC6520577. 4: Bossu A, Kostense A, Beekman HDM, Houtman MJC, van der Heyden MAG, Vos MA. Istaroxime, a positive inotropic agent devoid of proarrhythmic properties in sensitive chronic atrioventricular block dogs. Pharmacol Res. 2018 Jul;133:132-140. doi: 10.1016/j.phrs.2018.05.001. Epub 2018 May 16. PubMed PMID: 29753687. 5: Stagno MJ, Zacharopoulou N, Bochem J, Tsapara A, Pelzl L, Al-Maghout T, Kallergi G, Alkahtani S, Alevizopoulos K, Dimas K, Calogeropoulou T, Warmann SW, Lang F, Schmid E, Stournaras C. Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells. Cell Physiol Biochem. 2017;42(4):1366-1376. doi: 10.1159/000479200. Epub 2017 Jul 14. PubMed PMID: 28704809. 6: Wallner M, Khafaga M, Kolesnik E, Vafiadis A, Schwantzer G, Eaton DM, Curcic P, Köstenberger M, Knez I, Rainer PP, Pichler M, Pieske B, Lewinski DV. Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial functional effects in healthy and diseased human myocardium. Oncotarget. 2017 Jul 25;8(30):49264-49274. doi: 10.18632/oncotarget.17540. PubMed PMID: 28514771; PubMed Central PMCID: PMC5564766. 7: Alevizopoulos K, Dimas K, Papadopoulou N, Schmidt EM, Tsapara A, Alkahtani S, Honisch S, Prousis KC, Alarifi S, Calogeropoulou T, Lang F, Stournaras C. Functional characterization and anti-cancer action of the clinical phase II cardiac Na+/K+ ATPase inhibitor istaroxime: in vitro and in vivo properties and cross talk with the membrane androgen receptor. Oncotarget. 2016 Apr 26;7(17):24415-28. doi: 10.18632/oncotarget.8329. PubMed PMID: 27027435; PubMed Central PMCID: PMC5029711. 8: Ahmad S, Ahmad A, Hendry-Hofer TB, Loader JE, Claycomb WC, Mozziconacci O, Schöneich C, Reisdorph N, Powell RL, Chandler JD, Day BJ, Veress LA, White CW. Sarcoendoplasmic reticulum Ca(2+) ATPase. A critical target in chlorine inhalation-induced cardiotoxicity. Am J Respir Cell Mol Biol. 2015 Apr;52(4):492-502. doi: 10.1165/rcmb.2014-0005OC. PubMed PMID: 25188881; PubMed Central PMCID: PMC4491118. 9: George M, Rajaram M, Shanmugam E, VijayaKumar TM. Novel drug targets in clinical development for heart failure. Eur J Clin Pharmacol. 2014 Jul;70(7):765-74. doi: 10.1007/s00228-014-1671-4. Epub 2014 Apr 9. Review. PubMed PMID: 24710739. 10: Hohendanner F, Ljubojević S, MacQuaide N, Sacherer M, Sedej S, Biesmans L, Wakula P, Platzer D, Sokolow S, Herchuelz A, Antoons G, Sipido K, Pieske B, Heinzel FR. Intracellular dyssynchrony of diastolic cytosolic [Ca²⁺] decay in ventricular cardiomyocytes in cardiac remodeling and human heart failure. Circ Res. 2013 Aug 16;113(5):527-38. doi: 10.1161/CIRCRESAHA.113.300895. Epub 2013 Jul 3. PubMed PMID: 23825358. 11: Huang CL. SERCA2a stimulation by istaroxime: a novel mechanism of action with translational implications. Br J Pharmacol. 2013 Oct;170(3):486-8. doi: 10.1111/bph.12288. PubMed PMID: 23822610; PubMed Central PMCID: PMC3791988. 12: Ferrandi M, Barassi P, Tadini-Buoninsegni F, Bartolommei G, Molinari I, Tripodi MG, Reina C, Moncelli MR, Bianchi G, Ferrari P. Istaroxime stimulates SERCA2a and accelerates calcium cycling in heart failure by relieving phospholamban inhibition. Br J Pharmacol. 2013 Aug;169(8):1849-61. doi: 10.1111/bph.12278. PubMed PMID: 23763364; PubMed Central PMCID: PMC3753840. 13: Rudiger A, Singer M. The heart in sepsis: from basic mechanisms to clinical management. Curr Vasc Pharmacol. 2013 Mar 1;11(2):187-95. Review. PubMed PMID: 23506497. 14: Aditya S, Rattan A. Istaroxime: A rising star in acute heart failure. J Pharmacol Pharmacother. 2012 Oct;3(4):353-5. doi: 10.4103/0976-500X.103705. PubMed PMID: 23326115; PubMed Central PMCID: PMC3543564. 15: Gheorghiade M, Ambrosy AP, Ferrandi M, Ferrari P. Combining SERCA2a activation and Na-K ATPase inhibition: a promising new approach to managing acute heart failure syndromes with low cardiac output. Discov Med. 2011 Aug;12(63):141-51. Review. PubMed PMID: 21878191. 16: Luciani P, Fevre M, Leroux JC. Development and physico-chemical characterization of a liposomal formulation of istaroxime. Eur J Pharm Biopharm. 2011 Oct;79(2):285-93. doi: 10.1016/j.ejpb.2011.04.013. Epub 2011 Apr 29. PubMed PMID: 21550400. 17: Falk SA. Anesthetic considerations for the patient undergoing therapy for advanced heart failure. Curr Opin Anaesthesiol. 2011 Jun;24(3):314-9. doi: 10.1097/ACO.0b013e3283466692. Review. PubMed PMID: 21494131. 18: Farmakis D, Filippatos G. Istaroxime: is the remedy better than the disease?: Editorial to: "Chronic istaroxine improves cardiac function and heart rate variability in cardiomyopathic hamsters" by Pietro Lo Giudice et al. Cardiovasc Drugs Ther. 2011 Apr;25(2):115-7. doi: 10.1007/s10557-011-6295-7. PubMed PMID: 21484265. 19: Hasenfuss G, Teerlink JR. Cardiac inotropes: current agents and future directions. Eur Heart J. 2011 Aug;32(15):1838-45. doi: 10.1093/eurheartj/ehr026. Epub 2011 Mar 8. Review. PubMed PMID: 21388993. 20: Hoffman TM. Newer inotropes in pediatric heart failure. J Cardiovasc Pharmacol. 2011 Aug;58(2):121-5. doi: 10.1097/FJC.0b013e3182163ba0. Review. PubMed PMID: 21386708.