Page last updated: 2024-11-11

istaroxime

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Istaroxime: PST-2744 is the (E,Z)-isomer; a positive cardiac inotropic agent; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9841834
CHEMBL ID469045
SCHEMBL ID7285904
MeSH IDM0442365

Synonyms (27)

Synonym
st-2744 ,
istaroxime
pst-2744
debio-0614
CHEMBL469045 ,
5-alpha-androstan-6,17-dione, 3-((2-aminoethoxy)imino)-
w8i9h2tppl ,
unii-w8i9h2tppl
pst 2744
istaroxime [inn]
3-((2-aminoethoxy)imino)-5alpha-androstan-6,17-dione
HY-15718
CS-1531
SCHEMBL7285904
AKOS024259258
DB06157
androstane-3,6,17-trione, 3-(o-(2-aminoethyl)oxime), (3e,5.alpha.)-
203738-46-9
w40687go3s ,
istaroxime, (e)-
androstane-3,6,17-trione, 3-(o-(2-aminoethyl)oxime), (3e,5alpha)-
unii-w40687go3s
(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
AS-78198
DTXSID20870222
AC-36855
bdbm50605867

Research Excerpts

Overview

Istaroxime (ISTA) is a new Na(+),K(+)-ATPase inhibitor and SERCA(2) agonist. It stimulates cardiac contractility and relaxation in healthy and failing animal models and in patients with acute heart failure (AHF) syndrome.

ExcerptReferenceRelevance
"Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. "( Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells.
Al-Maghout, T; Alevizopoulos, K; Alkahtani, S; Bochem, J; Calogeropoulou, T; Dimas, K; Kallergi, G; Lang, F; Pelzl, L; Schmid, E; Stagno, MJ; Stournaras, C; Tsapara, A; Warmann, SW; Zacharopoulou, N, 2017
)
3.34
"Istaroxime is a new luso-inotropic compound that stimulates cardiac contractility and relaxation in healthy and failing animal models and in patients with acute heart failure (AHF) syndrome."( Istaroxime stimulates SERCA2a and accelerates calcium cycling in heart failure by relieving phospholamban inhibition.
Barassi, P; Bartolommei, G; Bianchi, G; Ferrandi, M; Ferrari, P; Molinari, I; Moncelli, MR; Reina, C; Tadini-Buoninsegni, F; Tripodi, MG, 2013
)
2.55
"Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase."( Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure.
Bianchetti, M; Blair, JE; Bubenek-Turconi, SI; Carminati, P; Ceracchi, M; Filippatos, GS; Gheorghiade, M; Korewicki, J; Kremastinos, D; Macarie, C; Ruzyllo, W; Sabbah, HN; Valentini, G, 2008
)
2.03
"Istaroxime (ISTA) is a new Na(+),K(+)-ATPase inhibitor and SERCA(2) agonist."( Sympathomimetic inefficiency in restoring contractility in the acute or chronic beta-blocker-treated ischaemic heart: comparison with a new agent.
Borsini, F; Carminati, P; Gagnol, JP; Loi, FM; Mattera, GG; Vanoli, E, 2008
)
1.07
"Istaroxime is a unique agent with both inotropic and lusitropic properties which is currently being studied for the treatment of AHFS."( Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na-K-ATPase inhibition: a new promising treatment for acute heart failure syndromes?
Blair, JE; Filippatos, GS; Gheorghiade, M; Harinstein, ME; Khan, H; Metra, M; Porchet, H; Sabbah, HN; Valentini, G; Vogel, M, 2009
)
2.52
"Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of the Na+/K+ adenosine triphosphatase and stimulation of sarcoplasmic reticulum calcium adenosine triphosphatase activity. "( Effects of istaroxime on diastolic stiffness in acute heart failure syndromes: results from the Hemodynamic, Echocardiographic, and Neurohormonal Effects of Istaroxime, a Novel Intravenous Inotropic and Lusitropic Agent: a Randomized Controlled Trial in P
Bianchetti, M; Blair, JE; Bubenek-Turconi, SI; Carminati, P; Ceracchi, M; Filippatos, GS; Gheorghiade, M; Grzybowski, J; Korewicki, J; Kremastinos, D; Macarie, C; Ruzyllo, W; Sabbah, HN; Shah, SJ; Valentini, G, 2009
)
2.19
"Istaroxime is a new luso-inotropic compound. "( Chronic istaroxime improves cardiac function and heart rate variability in cardiomyopathic hamsters.
Borsini, F; Gagnol, JP; Lo Giudice, P; Mattera, GG, 2011
)
2.25
"Istaroxime is a sodium-potassium adenosine triphosphatase (ATPase) inhibitor with the unique property of increasing sarcoplasmic reticulum calcium ATPase (SERCA) isoform 2a (SERCA2a) activity."( Istaroxime, a stimulator of sarcoplasmic reticulum calcium adenosine triphosphatase isoform 2a activity, as a novel therapeutic approach to heart failure.
Barassi, P; Bianchi, G; Ferrandi, M; Ferrari, P; Giacalone, G; Micheletti, R; Moro, B; Palazzo, F; Parodi, O; Schiavone, A, 2007
)
2.5
"Istaroxime is a new luso-inotropic compound selected for the treatment of acute heart failure syndromes, which reduces sodium-potassium adenosine triphosphatase (ATPase) activity and stimulates the sarcoplasmic calcium ATPase isoform 2 reuptake function. "( Istaroxime: a new luso-inotropic agent for heart failure.
Borsini, F; Carminati, P; Gagnol, JP; Lo Giudice, P; Loi, FM; Mattera, GG; Vanoli, E, 2007
)
3.23
"Istaroxime (PST2744) is a luso-inotrope that stimulates the sarcoplasmic reticulum calcium adenosine triphosphatase isoform 2a without chronotropic effects. "( A phase 1-2 dose-escalating study evaluating the safety and tolerability of istaroxime and specific effects on electrocardiographic and hemodynamic parameters in patients with chronic heart failure with reduced systolic function.
Amato, A; Carminati, P; Cowart, D; Ghali, JK; Gheorghiade, M; Haynos, W; Rayburn, BK; Smith, WB; Torre-Amione, G; Valentini, G; Zhang, D, 2007
)
2.01
"Istaroxime is a novel agent that, in animal models, has both inotropic (inhibition of the Na/K ATPase channel) and lusitropic (stimulation of sarcoplasmic reticulum calcium ATPase activity) effects."( Rationale and design of the hemodynamic, echocardiographic and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure (HORIZON-HF) trial.
Bacchieri, A; Bianchetti, M; Blair, JE; Filippatos, GS; Gheorghiade, M; Harinstein, ME; Macarie, C; Pang, PS; Ruzyllo, W; Sabbah, HN; Valentini, G,
)
1.07

Actions

ExcerptReferenceRelevance
"Istaroxime failed to increase SERCA activity in skeletal muscle microsomes devoid of phospholamban."( Modulation of sarcoplasmic reticulum function by PST2744 [istaroxime; (E,Z)-3-((2-aminoethoxy)imino) androstane-6,17-dione hydrochloride)] in a pressure-overload heart failure model.
Alemanni, M; Altomare, C; Barassi, P; Chisci, R; Ferrari, P; Micheletti, R; Mostacciuolo, G; Rocchetti, M; Zaza, A, 2008
)
1.31

Treatment

ExcerptReferenceRelevance
"Istaroxime-treatment preserved parasympathetic activity."( Chronic istaroxime improves cardiac function and heart rate variability in cardiomyopathic hamsters.
Borsini, F; Gagnol, JP; Lo Giudice, P; Mattera, GG, 2011
)
1.52

Toxicity

ExcerptReferenceRelevance
" An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects."( Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events?
Campia, U; Gheorghiade, M; Nodari, S, 2010
)
0.36
" There were 5 serious adverse events in Ista-1."( Safety and Efficacy of Istaroxime 1.0 and 1.5 µg/kg/min for Patients With Pre-Cardiogenic Shock.
Adamo, M; Chioncel, O; Cotter, G; Davison, B; Filippatos, G; Mebazaa, A; Metra, M; Novosadova, M; Pagnesi, M; Ponikowski, P; Simmons, P; Simonson, S; Soffer, J, 2023
)
1.22
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Sodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)IC50 (µMol)0.14000.00800.35800.5000AID1910714
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (2)

Processvia Protein(s)Taxonomy
regulation of sodium ion transportSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
establishment or maintenance of transmembrane electrochemical gradientSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
P-type sodium:potassium-exchanging transporter activitySodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
ATP bindingSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
ATP hydrolysis activitySodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
metal ion bindingSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
plasma membraneSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
plasma membraneSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
membraneSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
basolateral plasma membraneSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
axonSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
melanosomeSodium/potassium-transporting ATPase subunit alpha-1Canis lupus familiaris (dog)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (3)

Assay IDTitleYearJournalArticle
AID1910727Acute toxicity in iv dosed Albino Swiss CD-1 mouse assessed as lethal dose after 24 hrs
AID1910728Acute toxicity in po dosed Albino Swiss CD-1 mouse assessed as lethal dose after 24 hrs
AID1910714Inhibition of Beagle dog kidney NA+/K+ ATPase alpha 1 by measuring 32P-ATP hydrolysis preincubated for 10 mins followed by addition of 32P-ATP measured after 15 mins
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (47)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's22 (46.81)29.6817
2010's15 (31.91)24.3611
2020's10 (21.28)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 37.84

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index37.84 (24.57)
Research Supply Index4.01 (2.92)
Research Growth Index4.59 (4.65)
Search Engine Demand Index51.95 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (37.84)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (12.50%)5.53%
Reviews9 (18.75%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other33 (68.75%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]