ROSTAFUROXIN

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H34O4
Molecular Weight	374.5137
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@]12CC[C@H]3[C@@H](CC[C@@H]4C[C@@H](O)CC[C@]34C)[C@@]1(O)CC[C@]2(O)C5=COC=C5

InChI

InChIKey=AEAPORIZZWBIEX-DTBDINHYSA-N

InChI=1S/C23H34O4/c1-20-8-5-17(24)13-15(20)3-4-19-18(20)6-9-21(2)22(25,10-11-23(19,21)26)16-7-12-27-14-16/h7,12,14-15,17-19,24-26H,3-6,8-11,13H2,1-2H3/t15-,17+,18+,19-,20+,21-,22+,23+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11016814 | https://www.ncbi.nlm.nih.gov/pubmed/15570467 | https://www.ncbi.nlm.nih.gov/pubmed/10027844 | https://www.ncbi.nlm.nih.gov/pubmed/21235787

Rostafuroxin (PST 2238) is a digitoxygenin derivative, which selectively displaces ouabain from the Na ,K -ATPase receptor. PST 2238, at concentrations up to 10−4 M, did not show any significant interaction with a- and b-adrenergic, D1, D2, D3, 5-HT1, 5-HT2, H1, H2, M1, M2, A1, A2, Ca2 , Na , or K channel–associated receptors, AT1, AT2, ETa, ETb, GABA, thromboxane, vasopressin, angiotensin II, or the steorid-hormone receptors (androgen, progestogen, estrogen and mineralocorticoid), confirming that PST 2238 is specific for Na ,K -ATPase. Rostafuroxin has been developed in an attempt to unravel the contribution of mutated adducin and endogenous ouabain in the pathogenesis of hypertension. The compound lowered blood pressure in Milan hypertensive rats and humans. Rostafuroxine had been in phase II clinical trials for the treatment of hypertension. Following adverse events in Rostafuroxin group were described: dizziness, headache, upper respiratory tract infections, high blood pressure.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium-potassium adenosine triphosphatase 1 Target ID: Sodium-potassium adenosine triphosphatase Sources: https://www.ncbi.nlm.nih.gov/pubmed/10027844	Inhibitor 8504		1.5 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Essential hypertension 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16207152 https://www.ncbi.nlm.nih.gov/pubmed/21106941 https://www.ncbi.nlm.nih.gov/pubmed/21235787	Primary		Phase II 1147	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
0.05 mg multiple, oral Studied dose Dose: 0.05 mg Route: oral Route: multiple Dose: 0.05 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	Disc. AE: hypertension... AEs leading to discontinuation/dose reduction: hypertension (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/21235787
0.15 mg 1 times / day multiple, oral Studied dose Dose: 0.15 mg, 1 times / day Route: oral Route: multiple Dose: 0.15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	Disc. AE: hypertension... AEs leading to discontinuation/dose reduction: hypertension (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21235787
0.5 mg 1 times / day multiple, oral Studied dose Dose: 0.5 mg, 1 times / day Route: oral Route: multiple Dose: 0.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	Disc. AE: hypertension... AEs leading to discontinuation/dose reduction: hypertension (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21235787

AEs

AE	Significance	Dose	Population
hypertension	1 pt Disc. AE	0.05 mg multiple, oral Studied dose Dose: 0.05 mg Route: oral Route: multiple Dose: 0.05 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21235787
hypertension	3 patients Disc. AE	0.15 mg 1 times / day multiple, oral Studied dose Dose: 0.15 mg, 1 times / day Route: oral Route: multiple Dose: 0.15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21235787
hypertension	2 patients Disc. AE	0.5 mg 1 times / day multiple, oral Studied dose Dose: 0.5 mg, 1 times / day Route: oral Route: multiple Dose: 0.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21235787	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21235787

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001PDR	https://www.1pchem.com/search?query=1P001PDR
AChemBlock	10371	http://www.achemblock.com/catalogsearch/result/?q=10371
AK Scientific	4016AH	https://aksci.com/item_detail.php?cat=4016AH
Angene	AGN-PC-0WHEEK	http://www.angenechemical.com/productshow/AGN-PC-0WHEEK.html
ApexBio Technology	B5894	https://www.apexbt.com/catalogsearch/result/?q=B5894
BLD Pharm	BD293274	http://www.bldpharm.com/search/Search.html?keyword=BD293274
Cayman Chemical	21282	http://www.caymanchem.com/app/template/Product.vm/catalog/21282
Chem Scene	CS-3295	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3295
ChemShuttle	157211	https://www.chemshuttle.com/catalogsearch/result/?q=157211
Excenen	EX-A192	http://www.excenen.com/searchresultlist.php?id=EX-A192
Lab Network	LN01343089	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343089
mcule	MCULE-5222011463	https://mcule.com/MCULE-5222011463/
mcule	MCULE-6501596414	https://mcule.com/MCULE-6501596414/
MedChem Express	HY-12283	https://www.medchemexpress.com/search.html?q=HY-12283&ft=&fa=&fp=
Molnova	M12236	https://www.molnova.com/en/serch-list.html?keywords=M12236
MolPort	MolPort-035-765-992	https://www.molport.com/shop/molecule-link/MolPort-035-765-992
MuseChem	I001990	https://www.musechem.com/product/I001990.html
ShangHai Biochempartner	BCP000970	http://www.biochempartner.com/search_BCP000970
TargetMol	T2621	https://www.targetmol.com/search?keyword=T2621
Tocris	5315	https://www.tocris.com/search.php?Type=QuickSearch&Value=5315

PubMed

Title	Date	PubMed
Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 2: clinical studies.	2010-11-24	21106941
PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension.	1999-03	10027844
PST2238: a new antihypertensive compound that antagonizes the long-term pressor effect of ouabain.	1998-04	9535997
Role of ouabain-like compound in the regulation of transmembrane sodium and potassium gradients in rats.	1997-09	9323018
17 beta-(3-furyl)-5 beta-androstane-3 beta, 14 beta, 17 alpha-triol (PST 2238). A very potent antihypertensive agent with a novel mechanism of action.	1997-05-23	9171865

Patents

Sample Use Guides

In Vivo Use Guide

0.05, 0.15, 0.5, 1.5, or 5.0 mg/day

Route of Administration: Oral

In Vitro Use Guide

To assess the long-term effect of low concentrations of PST 2238 on the Na+ -K+ pump activity, NRK cells were incubated with PST 2238 for 5 d. PST 2238 stimulated the pump at 10(−6) M (26%, n.s.) and 10(−5) M (27%, p < 0.05).

Name

Type

Language

21,23-EPOXY-24-NOR-14.BETA.,5.BETA.-CHOLA-20,21-DIENE-3.BETA.,14,17.ALPHA.-TRIOL

Preferred Name

English

ROSTAFUROXIN

Official Name

English

rostafuroxin [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C270