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Details

Stereochemistry ACHIRAL
Molecular Formula C22H25N3O4
Molecular Weight 395.4516
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VESNARINONE

SMILES

COC1=C(OC)C=C(C=C1)C(=O)N2CCN(CC2)C3=CC=C4NC(=O)CCC4=C3

InChI

InChIKey=ZVNYJIZDIRKMBF-UHFFFAOYSA-N
InChI=1S/C22H25N3O4/c1-28-19-7-3-16(14-20(19)29-2)22(27)25-11-9-24(10-12-25)17-5-6-18-15(13-17)4-8-21(26)23-18/h3,5-7,13-14H,4,8-12H2,1-2H3,(H,23,26)

HIDE SMILES / InChI

Molecular Formula C22H25N3O4
Molecular Weight 395.4516
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/9420657

Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. In Japan, vesnarinone was approved in June 1990 and first marketed in September 1990.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.2 µM [IC50]
1.096 µM [IC50]
10.4 µM [IC50]
13.2 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Arkin-Z

Approved Use

Heart failure

Launch Date

1990
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
In vitro and in vivo studies of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), a novel positive inotropic drug, in various animals.
1984
Vesnarinone inhibits production of HIV-1 in cultured cells.
1993 Sep 30
Differential modulation of cytokine production by drugs: implications for therapy in heart failure.
1996 Dec
Open channel block of HERG K(+) channels by vesnarinone.
2001 Aug
Interferon-alpha 2b and vesnarinone influence levels of tumor necrosis factor-alpha, apoptosis, or interleukin 6 in ESKOL, a hairy cell leukemic cell line. A potential cytokine and oncogene relationship regulating apoptosis is suggested.
2002 Feb
Inotropic agents and immune modulation.
2002 May
Induction of apoptosis in human choriocarcinoma cell lines by treatment with 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (vesnarinone).
2002 Nov-Dec
Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line.
2002 Oct 21
Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort.
2003 Feb 5
Vesnarinone: a differentiation-inducing anti-cancer drug.
2003 Jul
Transcriptional activation of cyclin-dependent kinase inhibitor, p21waf1 gene by treatment with a differentiation inducing agent, vesnarinone in a human salivary gland cancer cell line.
2003 Mar
Role of nonglycosidic inotropic agents: indications, ethics, and limitations.
2003 Mar
[Inotropic agents].
2003 May
Extended application of an LC-MS/MS method for the analysis of vesnarinone and its metabolites in human urine and dialysate fluid.
2003 Nov 24
Optimising outcomes in end-stage heart failure: differences in therapeutic responses between diverse ethnic groups.
2004
Precautions for use and adverse effects of vesnarinone: potential mechanisms and future therapies.
2004
Clinical characteristics of vesnarinone.
2004
The best of times, the worst of times: the wealth and poverty of heart failure pharmacotherapies: is there a role for vesnarinone?
2004
New positive inotropic agents in the treatment of left ventricular dysfunction.
2004 Jun
Comparison of kinetic properties of quinidine and dofetilide block of HERG channels.
2004 Jun 16
Models of dilated cardiomyopathy in small animals and novel positive inotropic therapies.
2004 May
TSC-22 (TGF-beta stimulated clone-22): a novel molecular target for differentiation-inducing therapy in salivary gland cancer.
2004 Sep
Frequent downregulation of 14-3-3 sigma protein and hypermethylation of 14-3-3 sigma gene in salivary gland adenoid cystic carcinoma.
2004 Sep 13
Vesnarinone-mediated alterations of gene expression in cardiac fibroblasts from aortic regurgitant hearts.
2004 Sep-Oct
Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis.
2005
Vesnarinone inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing the expression of vascular endothelial growth factor and interleukin-8.
2005 Dec
Treating critical illness: the importance of first doing no harm.
2005 Jun
A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo.
2005 Sep
Differentiation-inducing therapy for solid tumors.
2006
Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity--a common inflammatory phenotype?
2006 May 2
Effects of promyelocytic leukemia zinc finger protein on the proliferation of cultured human corneal endothelial cells.
2007 Apr 27
Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials.
2007 Apr 3
Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.
2007 Dec 10
Effects of phosphodiesterase (PDE) inhibitors on human ether-a-go-go related gene (hERG) channel activity.
2007 Jan-Feb
Frequency-dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model.
2007 Jul
Placebo effect-adjusted assessment of quality of life in placebo-controlled clinical trials.
2008 Apr 30
Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth.
2008 Jan 28
In silico risk assessment for drug-induction of cardiac arrhythmia.
2008 Sep
Comparative value of simple inflammatory markers in the prediction of left ventricular systolic dysfunction in postacute coronary syndrome patients.
2009
Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin.
2009
Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities.
2009
Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells.
2009 Aug 12
Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond.
2009 Dec
Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials.
2009 Dec
A novel approach to improve cardiac performance: cardiac myosin activators.
2009 Dec
Leukocyte redistribution: effects of beta blockers in patients with chronic heart failure.
2009 Jul 29
Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders.
2009 Nov 12
β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices.
2010 Dec 20
Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors.
2010 Jan 15
Effect of levosimendan in experimental verapamil-induced myocardial depression.
2010 Mar 11
Patents

Patents

Sample Use Guides

In Vivo Use Guide
60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure
Route of Administration: Oral
In Vitro Use Guide
Vesnarinone (0–300 uM) inhibits tumor necrosis factor (TNF)a-induced expression of nuclear factor kB target genes in 293T cells
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:33:20 GMT 2023
Edited
by admin
on Fri Dec 15 15:33:20 GMT 2023
Record UNII
5COW40EV8M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VESNARINONE
INN   JAN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
VESNARINONE [MART.]
Common Name English
ARKIN Z
Brand Name English
VESNARINONE [JAN]
Common Name English
Vesnarinone [WHO-DD]
Common Name English
vesnarinone [INN]
Common Name English
OPC-8212
Code English
VESNARINONE [MI]
Common Name English
VESNARINONE [USAN]
Common Name English
VESNARINONE [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C259
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
NCI_THESAURUS C744
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
Code System Code Type Description
MERCK INDEX
m11436
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID80231411
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
DRUG BANK
DB12082
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
USAN
Z-20
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
ChEMBL
CHEMBL17423
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
WIKIPEDIA
VESNARINONE
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
FDA UNII
5COW40EV8M
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
PUBCHEM
5663
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
NCI_THESAURUS
C1415
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
MESH
C041667
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
DRUG CENTRAL
2817
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
EVMPD
SUB00045MIG
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
SMS_ID
100000079102
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
CAS
81840-15-5
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
INN
6108
Created by admin on Fri Dec 15 15:33:21 GMT 2023 , Edited by admin on Fri Dec 15 15:33:21 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY