Page last updated: 2024-12-08

enrasentan

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

Description

enrasentan: decreases ischemic brain injury; an endothelin A and B receptor antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

enrasentan : A member of the class of indanes that is 2,3-dihydro-1H-indene which is substituted by a 1,3-benzodioxol-5-yl group, carboxy group, 2-(2-hydroxyethoxy)-4-methoxyphenyl group and a propoxy group at positions 1S, 2R, 3S and 5, respectively. It is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. The drug was being developed by GSK for the treatment of congestive heart failure and pulmonary hypertension (clinical trials discontinued). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID178103
CHEMBL ID431651
CHEBI ID156258
SCHEMBL ID1649828
MeSH IDM0258216

Synonyms (28)

Synonym
3-(2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-carboxylic acid
167256-08-8
sb-217242
enrasentan
sb 217242
PDSP2_001716
(1s,2r,3s)-3-(2-(2-hydroxyethoxy)-4-methoxyphenyl)-1-(3,4-(methylenedioxy)phenyl)-5-propoxy-2-indancarboxylic acid
(1s,2r,3s)-1-(1,3-benzodioxol-5-yl)-3-[2-(2-hydroxyethoxy)-4-methoxyphenyl]-5-propoxy-2,3-dihydro-1h-indene-2-carboxylic acid
enrasentanum
CHEBI:156258
sb217242
CHEMBL431651 ,
(1s,2r,3s)-1-benzo[1,3]dioxol-5-yl-3-[2-(2-hydroxy-ethoxy)-4-methoxy-phenyl]-5-propoxy-indan-2-carboxylic acid
bdbm50061077
qg16h8a6zh ,
enrasentan [inn]
unii-qg16h8a6zh
SCHEMBL1649828
(1s, 2r, 3s)-3-[2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl]-1-(3,4-methylendioxyphenyl)-5-propoxyindane-2-carboxylic acid
GLCKXJLCYIJMRB-UPRLRBBYSA-N
(+) (1s, 2r, 3s)-3-[2-(2-hydroxyeth-1-yloxy)-4methoxyphenyl]-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid
(1s, 2r, 3s)-3-[2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl)-1-(3,4-methylendioxyphenyl)-5-propoxyindane-2-carboxylic acid
(+) (1s, 2r, 3s)-3-[2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl]-1-(3,4-methylenedioxyphenyl)-5-propoxyindane-2-carboxylic acid
DTXSID50168260
DB06460
Q27287239
1h-indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-2,3-dihydro-3-[2-(2-hydroxyethoxy)-4-methoxyphenyl]-5-propoxy-, (1s,2r,3s)-
AKOS040751689

Research Excerpts

Overview

Enrasentan is an antagonist of endothelin (ET) receptors. It has a higher affinity for ET(A) receptors, although it cannot be considered a selective antagonist.

ExcerptReferenceRelevance
"Enrasentan is a mixed ET(A) and ET(B) receptor antagonist with a higher affinity for ET(A) receptors, although it cannot be considered a selective antagonist."( Enrasentan, an antagonist of endothelin receptors.
Cosenzi, A, 2003
)
2.48
"Enrasentan is an antagonist of endothelin (ET) receptors. "( Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia.
Bellini, G; Bernobich, E; Bertola, G; Bonavita, M; Cosenzi, A; Trevisan, R, 2002
)
2.04

Effects

ExcerptReferenceRelevance
"Enrasentan has been added to conventional treatment in patients with heart failure (NYHA Class 2-3) and no addictive effect of the drug has been observed."( Enrasentan, an antagonist of endothelin receptors.
Cosenzi, A, 2003
)
2.48

Treatment

ExcerptReferenceRelevance
"Enrasentan-treated groups exhibited significantly improved survival (90-95% vs."( Enrasentan improves survival, limits left ventricular remodeling, and preserves myocardial performance in hypertensive cardiac hypertrophy and dysfunction.
Aiyar, N; Anderson, KM; Barone, FC; Coatney, RW; Nelson, AH; Ohlstein, EH; Olzinski, AR; Willette, RN; Woods, T, 2001
)
2.47

Bioavailability

ExcerptReferenceRelevance
"This study describes the pharmacological characterization of SB 217242, a highly potent orally bioavailable nonpeptide antagonist of both endothelin type A (ETA) and endothelin type B (ETB) receptors."( Nonpeptide endothelin receptor antagonists. VI: Pharmacological characterization of SB 217242, a potent and highly bioavailable endothelin receptor antagonist.
Beck, G; Eddy, EP; Ellens, H; Elliott, JD; Fong, KL; Hay, DW; Lago, A; Nambi, P; Ohlstein, EH; Smith, P, 1996
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
endothelin receptor antagonistA hormone antagonist that blocks endothelin receptors.
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (6)

ClassDescription
monocarboxylic acidAn oxoacid containing a single carboxy group.
benzodioxoles
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
indanes
monomethoxybenzeneCompounds containing a benzene skeleton substituted with one methoxy group.
primary alcoholA primary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has either three hydrogen atoms attached to it or only one other carbon atom and two hydrogen atoms attached to it.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Endothelin receptor type BHomo sapiens (human)Ki0.11050.00010.05430.3710AID66360; AID66692
Endothelin-1 receptorHomo sapiens (human)Ki0.00110.00000.430010.0000AID68296; AID68489
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (109)

Processvia Protein(s)Taxonomy
negative regulation of transcription by RNA polymerase IIEndothelin receptor type BHomo sapiens (human)
neural crest cell migrationEndothelin receptor type BHomo sapiens (human)
positive regulation of protein phosphorylationEndothelin receptor type BHomo sapiens (human)
renin secretion into blood streamEndothelin receptor type BHomo sapiens (human)
regulation of heart rateEndothelin receptor type BHomo sapiens (human)
regulation of pHEndothelin receptor type BHomo sapiens (human)
cell surface receptor signaling pathwayEndothelin receptor type BHomo sapiens (human)
negative regulation of adenylate cyclase activityEndothelin receptor type BHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayEndothelin receptor type BHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationEndothelin receptor type BHomo sapiens (human)
nervous system developmentEndothelin receptor type BHomo sapiens (human)
peripheral nervous system developmentEndothelin receptor type BHomo sapiens (human)
posterior midgut developmentEndothelin receptor type BHomo sapiens (human)
positive regulation of cell population proliferationEndothelin receptor type BHomo sapiens (human)
gene expressionEndothelin receptor type BHomo sapiens (human)
negative regulation of neuron maturationEndothelin receptor type BHomo sapiens (human)
response to organic cyclic compoundEndothelin receptor type BHomo sapiens (human)
vein smooth muscle contractionEndothelin receptor type BHomo sapiens (human)
calcium-mediated signalingEndothelin receptor type BHomo sapiens (human)
cGMP-mediated signalingEndothelin receptor type BHomo sapiens (human)
heparin metabolic processEndothelin receptor type BHomo sapiens (human)
melanocyte differentiationEndothelin receptor type BHomo sapiens (human)
regulation of fever generationEndothelin receptor type BHomo sapiens (human)
aldosterone metabolic processEndothelin receptor type BHomo sapiens (human)
enteric smooth muscle cell differentiationEndothelin receptor type BHomo sapiens (human)
positive regulation of urine volumeEndothelin receptor type BHomo sapiens (human)
renal sodium excretionEndothelin receptor type BHomo sapiens (human)
epithelial fluid transportEndothelin receptor type BHomo sapiens (human)
vasoconstrictionEndothelin receptor type BHomo sapiens (human)
vasodilationEndothelin receptor type BHomo sapiens (human)
negative regulation of apoptotic processEndothelin receptor type BHomo sapiens (human)
positive regulation of canonical NF-kappaB signal transductionEndothelin receptor type BHomo sapiens (human)
macrophage chemotaxisEndothelin receptor type BHomo sapiens (human)
response to painEndothelin receptor type BHomo sapiens (human)
enteric nervous system developmentEndothelin receptor type BHomo sapiens (human)
regulation of epithelial cell proliferationEndothelin receptor type BHomo sapiens (human)
negative regulation of protein metabolic processEndothelin receptor type BHomo sapiens (human)
canonical Wnt signaling pathwayEndothelin receptor type BHomo sapiens (human)
positive regulation of penile erectionEndothelin receptor type BHomo sapiens (human)
establishment of endothelial barrierEndothelin receptor type BHomo sapiens (human)
renal sodium ion absorptionEndothelin receptor type BHomo sapiens (human)
calcium ion transmembrane transportEndothelin receptor type BHomo sapiens (human)
cellular response to lipopolysaccharideEndothelin receptor type BHomo sapiens (human)
protein transmembrane transportEndothelin receptor type BHomo sapiens (human)
podocyte differentiationEndothelin receptor type BHomo sapiens (human)
endothelin receptor signaling pathwayEndothelin receptor type BHomo sapiens (human)
renal albumin absorptionEndothelin receptor type BHomo sapiens (human)
neuroblast migrationEndothelin receptor type BHomo sapiens (human)
chordate pharynx developmentEndothelin receptor type BHomo sapiens (human)
response to sodium phosphateEndothelin receptor type BHomo sapiens (human)
response to endothelinEndothelin receptor type BHomo sapiens (human)
developmental pigmentationEndothelin receptor type BHomo sapiens (human)
mitotic cell cycleEndothelin-1 receptorHomo sapiens (human)
branching involved in blood vessel morphogenesisEndothelin-1 receptorHomo sapiens (human)
response to hypoxiaEndothelin-1 receptorHomo sapiens (human)
in utero embryonic developmentEndothelin-1 receptorHomo sapiens (human)
blood vessel remodelingEndothelin-1 receptorHomo sapiens (human)
response to amphetamineEndothelin-1 receptorHomo sapiens (human)
regulation of heart rateEndothelin-1 receptorHomo sapiens (human)
glomerular filtrationEndothelin-1 receptorHomo sapiens (human)
cardiac chamber formationEndothelin-1 receptorHomo sapiens (human)
left ventricular cardiac muscle tissue morphogenesisEndothelin-1 receptorHomo sapiens (human)
atrial cardiac muscle tissue developmentEndothelin-1 receptorHomo sapiens (human)
cardiac neural crest cell migration involved in outflow tract morphogenesisEndothelin-1 receptorHomo sapiens (human)
noradrenergic neuron differentiationEndothelin-1 receptorHomo sapiens (human)
intracellular calcium ion homeostasisEndothelin-1 receptorHomo sapiens (human)
smooth muscle contractionEndothelin-1 receptorHomo sapiens (human)
mitochondrion organizationEndothelin-1 receptorHomo sapiens (human)
signal transductionEndothelin-1 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayEndothelin-1 receptorHomo sapiens (human)
activation of adenylate cyclase activityEndothelin-1 receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayEndothelin-1 receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayEndothelin-1 receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationEndothelin-1 receptorHomo sapiens (human)
respiratory gaseous exchange by respiratory systemEndothelin-1 receptorHomo sapiens (human)
regulation of blood pressureEndothelin-1 receptorHomo sapiens (human)
cell population proliferationEndothelin-1 receptorHomo sapiens (human)
response to woundingEndothelin-1 receptorHomo sapiens (human)
gene expressionEndothelin-1 receptorHomo sapiens (human)
protein kinase A signalingEndothelin-1 receptorHomo sapiens (human)
regulation of glucose transmembrane transportEndothelin-1 receptorHomo sapiens (human)
neural crest cell fate commitmentEndothelin-1 receptorHomo sapiens (human)
artery smooth muscle contractionEndothelin-1 receptorHomo sapiens (human)
neuron remodelingEndothelin-1 receptorHomo sapiens (human)
heparin metabolic processEndothelin-1 receptorHomo sapiens (human)
thyroid gland developmentEndothelin-1 receptorHomo sapiens (human)
cellular response to oxidative stressEndothelin-1 receptorHomo sapiens (human)
embryonic heart tube developmentEndothelin-1 receptorHomo sapiens (human)
aorta developmentEndothelin-1 receptorHomo sapiens (human)
vasoconstrictionEndothelin-1 receptorHomo sapiens (human)
norepinephrine metabolic processEndothelin-1 receptorHomo sapiens (human)
middle ear morphogenesisEndothelin-1 receptorHomo sapiens (human)
positive regulation of canonical NF-kappaB signal transductionEndothelin-1 receptorHomo sapiens (human)
cellular response to human chorionic gonadotropin stimulusEndothelin-1 receptorHomo sapiens (human)
enteric nervous system developmentEndothelin-1 receptorHomo sapiens (human)
sympathetic nervous system developmentEndothelin-1 receptorHomo sapiens (human)
axon extensionEndothelin-1 receptorHomo sapiens (human)
embryonic skeletal system developmentEndothelin-1 receptorHomo sapiens (human)
neuromuscular processEndothelin-1 receptorHomo sapiens (human)
sodium ion homeostasisEndothelin-1 receptorHomo sapiens (human)
canonical Wnt signaling pathwayEndothelin-1 receptorHomo sapiens (human)
face developmentEndothelin-1 receptorHomo sapiens (human)
axonogenesis involved in innervationEndothelin-1 receptorHomo sapiens (human)
establishment of endothelial barrierEndothelin-1 receptorHomo sapiens (human)
pharyngeal arch artery morphogenesisEndothelin-1 receptorHomo sapiens (human)
renal sodium ion absorptionEndothelin-1 receptorHomo sapiens (human)
calcium ion transmembrane transportEndothelin-1 receptorHomo sapiens (human)
cellular response to follicle-stimulating hormone stimulusEndothelin-1 receptorHomo sapiens (human)
cellular response to luteinizing hormone stimulusEndothelin-1 receptorHomo sapiens (human)
protein transmembrane transportEndothelin-1 receptorHomo sapiens (human)
glomerular endothelium developmentEndothelin-1 receptorHomo sapiens (human)
podocyte differentiationEndothelin-1 receptorHomo sapiens (human)
endothelin receptor signaling pathway involved in heart processEndothelin-1 receptorHomo sapiens (human)
renal albumin absorptionEndothelin-1 receptorHomo sapiens (human)
vascular associated smooth muscle cell developmentEndothelin-1 receptorHomo sapiens (human)
mesenchymal cell apoptotic processEndothelin-1 receptorHomo sapiens (human)
sympathetic neuron axon guidanceEndothelin-1 receptorHomo sapiens (human)
semaphorin-plexin signaling pathway involved in axon guidanceEndothelin-1 receptorHomo sapiens (human)
podocyte apoptotic processEndothelin-1 receptorHomo sapiens (human)
meiotic cell cycle process involved in oocyte maturationEndothelin-1 receptorHomo sapiens (human)
cranial skeletal system developmentEndothelin-1 receptorHomo sapiens (human)
response to acetylcholineEndothelin-1 receptorHomo sapiens (human)
regulation of protein localization to cell leading edgeEndothelin-1 receptorHomo sapiens (human)
positive regulation of cation channel activityEndothelin-1 receptorHomo sapiens (human)
endothelin receptor signaling pathwayEndothelin-1 receptorHomo sapiens (human)
developmental pigmentationEndothelin-1 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
endothelin receptor activityEndothelin receptor type BHomo sapiens (human)
protein bindingEndothelin receptor type BHomo sapiens (human)
peptide hormone bindingEndothelin receptor type BHomo sapiens (human)
type 1 angiotensin receptor bindingEndothelin receptor type BHomo sapiens (human)
phosphatidylinositol phospholipase C activityEndothelin-1 receptorHomo sapiens (human)
endothelin receptor activityEndothelin-1 receptorHomo sapiens (human)
protein bindingEndothelin-1 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneEndothelin receptor type BHomo sapiens (human)
nuclear membraneEndothelin receptor type BHomo sapiens (human)
plasma membraneEndothelin receptor type BHomo sapiens (human)
plasma membraneEndothelin-1 receptorHomo sapiens (human)
plasma membraneEndothelin-1 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID66692Tested for binding affinity for human Endothelin B receptor by measuring its ability to displace [125I]-ET-3 from chinese hamster ovary cells(CHO)1998Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546).
AID66854Ratio of endothelin A receptor and endothelin B receptor.1997Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
AID25914Half-life is obtained after intravenous dosing of rats.1997Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
AID23605Pharmacokinetic profile-half life was evaluated in rats upon intravenous administration1998Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546).
AID68489Tested for binding affinity for human Endothelin A receptor by measuring its ability to displace [125I]-ET-1 from chinese hamster ovary cells(CHO)1998Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546).
AID68296Ability to displace endothelin ([125I]ET1) from human Endothelin A receptor1997Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
AID18622Bioavailability in rat1998Journal of medicinal chemistry, Aug-13, Volume: 41, Issue:17
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546).
AID18193Oral bioavailability in rat1997Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
AID66360Ability to displace endothelin ([125I]ET1) from human Endothelin B receptor1997Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (31)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's17 (54.84)18.2507
2000's14 (45.16)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 15.91

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index15.91 (24.57)
Research Supply Index3.56 (2.92)
Research Growth Index4.28 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (15.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (6.25%)5.53%
Reviews6 (18.75%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other24 (75.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]