ISTAROXIME

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23326115 | https://www.ncbi.nlm.nih.gov/pubmed/27027435 | http://adisinsight.springer.com/drugs/800012030

Istaroxime is a novel intravenous agent with luso-inotropic properties that acts by inhibition of Na( )/K( ) adenosine triphosphatase and stimulation of sarco/ endoplasmic reticulum calcium ATPase isoform 2. It is significantly decreased left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, heart rate and increased systolic blood pressure and cardiac index with no change in neurohormones, renal function or troponin I. Istaroxime has successfully concluded phase II clinical trials in cardiac failure patients. Istaroxime induced apoptosis, affected the key proliferative and apoptotic mediators c-Myc and caspase-3 and modified actin cytoskeleton dynamics and RhoA activity in prostate cancer cells – this provides novel insights into the anti-cancer properties of istaroxime further supporting the development of this agent as a novel anti-cancer drug candidate.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 5 Target ID: CHEMBL3901 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17239701 \| https://www.ncbi.nlm.nih.gov/pubmed/23326115	Activator 1430	2.5 nM [EC50]
Na+/K+-ATPase (dog) 2 Target ID: Na+/K+-ATPase (dog) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12388640	Inhibitor 8297	0.43 µM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27027435	Binding Agent 1064
Apoptosis 155 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27027435	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Heart failure 103 Sources: https://clinicaltrials.gov/ct2/show/NCT00838253 https://www.ncbi.nlm.nih.gov/pubmed/19464414 https://www.ncbi.nlm.nih.gov/pubmed/18534276	Primary		Phase II 1132	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27027435	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
14.46 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17239705/	0.5 μg/kg/min 1 times / hour single, intravenous dose: 0.5 μg/kg/min route of administration: Intravenous experiment type: SINGLE co-administered:		ISTAROXIME plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
90.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17239705/	5 μg/kg/min single, intravenous dose: 5 μg/kg/min route of administration: Intravenous experiment type: SINGLE co-administered:		ISTAROXIME plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
18.3 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17239705/	5 μg/kg/min single, intravenous dose: 5 μg/kg/min route of administration: Intravenous experiment type: SINGLE co-administered:		ISTAROXIME plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17239705/	3.33 μg/kg/min single, intravenous dose: 3.33 μg/kg/min route of administration: Intravenous experiment type: SINGLE co-administered:		ISTAROXIME plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	Disc. AE: Arrhythmia, Nausea... Other AEs: Cardiac failure, ventricular tachycardia... AEs leading to discontinuation/dose reduction: Arrhythmia (2.5%) Nausea (2.5%) vomiting (2.5%) Other AEs: Cardiac failure (17.5%) ventricular tachycardia (17.5%) Infusion site pain (32.5%) arrhythmia (17.5%) atrial fibrillatio (17.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/31975496

AEs

AE	Significance	Dose	Population
Cardiac failure	17.5%	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
arrhythmia	17.5%	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
atrial fibrillatio	17.5%	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
ventricular tachycardia	17.5%	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
Arrhythmia	2.5% Disc. AE	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
Nausea	2.5% Disc. AE	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
vomiting	2.5% Disc. AE	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496
Infusion site pain	32.5%	1 ug/kg/min single, intravenous (unknown) Studied dose Dose: 1 ug/kg/min Route: intravenous Route: single Dose: 1 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31975496	unhealthy, ADULT n = 40 Health Status: unhealthy Condition: acute heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/31975496

Sourcing

Vendor/Aggregator	ID	URL
AKOS	AKOS028109342	http://akoscompounds.de/catalogue/AKosSamplesiSSretrieval.php?GUID=4e4caa52-3dca-4da0-b75a-caeae59e1096&IDNUMBERS=AKOS028109342
mcule	MCULE-6231969302	https://mcule.com/MCULE-6231969302/

PubMed

Title	Date	PubMed
Sarcoendoplasmic reticulum Ca(2+) ATPase. A critical target in chlorine inhalation-induced cardiotoxicity.	2015 Apr	25188881

Patents

Sample Use Guides

In Vivo Use Guide

0.5 or 1.0 or 1.5 ug/kg body weight/minute for six hours

Route of Administration: Intravenous

In Vitro Use Guide

Istaroxime (5 uM) over a period of 24 hours increased the number of apoptotic cells in DU145 prostate cancer cells culture from 9.48% in control samples to 46.54% following treatment.

Substance Class	Mixture Created by `admin` on `Sat Dec 16 15:21:21 UTC 2023` Edited by `admin` on `Sat Dec 16 15:21:21 UTC 2023`
Record UNII	W8I9H2TPPL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ISTAROXIME

Official Name

English

ANDROSTANE-3,6,17-TRIONE, 3-(O-(2-AMINOETHYL)OXIME), (5.ALPHA.)-

Systematic Name

English

PST-2744

Code

English

istaroxime [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78322