Page last updated: 2024-12-07

tak 044

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

Description

TAK 044: endothelin receptor antagonist [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID123882
CHEMBL ID61425
MeSH IDM0233441

Synonyms (8)

Synonym
tak 044
tak-044
CHEMBL61425 ,
157380-72-8
cyclo(d-alpha-aspartyl-3-((4-phenylpiperazin-1-yl)carbonyl)-l-alanyl-l-alpha-aspartyl-d-2-(2-thienyl)glycyl-l-leucyl-d-tryptophyl) disodium salt
cyclo(l-alpha-aspartyl-(2r)-2-(2-thienyl)glycyl-l-leucyl-d tryptophyl-d-alpha-aspartyl-(alpha-s)-alpha-amino-gamma-oxo-4-phenyl-1-piperazinebutanoyl), disodium salt
cyclo(4-oxo-4-(4-phenyl-1-piperazinyl)-l-2-aminobutanoyl-l-alpha-aspartyl-d-2-(2-thienyl)glycyl-l-leucyl-d-tryptophyl-d-alpha-aspartyl), disodium salt
disodium;2-[(2r,5s,8s,11s,14s,17r)-8-(carboxylatomethyl)-17-(1h-indol-3-ylmethyl)-14-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-5-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]-11-thiophen-2-yl-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetate

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The primary end point was whether a delayed ischemic event occurred within 3 months after the first dose of the study drug and the secondary end points included determining whether a delayed ischemic event occurred by 10 days after the first dose of the study drug, whether a new cerebral infarct was demonstrated on a computerized tomography scan or at postmortem examination by 3 months after administration of the initial dose, the patient's Glasgow Outcome Scale scores at 3 months after the initial dose, and adverse events."( Efficacy and safety of the endothelin, receptor antagonist TAK-044 in treating subarachnoid hemorrhage: a report by the Steering Committee on behalf of the UK/Netherlands/Eire TAK-044 Subarachnoid Haemorrhage Study Group.
Bell, BA; Murray, GD; Pickard, JD; Shaw, MD; Teasdale, GM; Vermeulen, M, 2000
)
0.31

Pharmacokinetics

ExcerptReferenceRelevance
"The pharmacokinetic interaction between TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium, CAS 157380-72-8) and ciclosporin (CAS 59865-13-3) was investigated after concomitant intravenous (i."( Pharmacokinetic interaction between TAK-044, a new endothelin antagonist, and ciclosporin in rats.
Maeshiba, Y; Tsukuda, R; Yamashita, K; Yoshimura, Y, 2002
)
0.31

Bioavailability

ExcerptReferenceRelevance
" Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships."( Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
Berens, KL; Blok, N; Bourgoyne, AR; Brock, TA; Bui, H; Decker, ER; Dixon, RA; Holland, GW; Knowles, V; Wang, J; Wu, C; You, TJ, 2004
)
0.32

Dosage Studied

ExcerptRelevanceReference
" ET-1 and ET-3 increased perfusion pressure in isolated kidney preparations with similar potency, indicating that the renal vasoconstriction evoked by these ET isomers is mainly via ETB receptors, and TAK-044 (10nM) shifted the ET-1 dose-response curve to the right by a factor about 10."( Effects of a new endothelin antagonist, TAK-044, on post-ischemic acute renal failure in rats.
Fujino, M; Kandori, H; Kitayoshi, T; Kubo, K; Kusumoto, K; Sato, S; Wakimasu, M; Watanabe, T, 1994
)
0.29
" In the absence of a dose-response relation, TAK-044 patients were analyzed as a single group."( Systemic, pulmonary, and renal hemodynamic effects of endothelin ET(A/B)-receptor blockade in patients with maintained left ventricular function.
Bianchetti, MG; Binggeli, C; Fleisch, M; Kiowski, W; Lüscher, TF; Meier, B; Sütsch, G; Wenzel, RR; Yan, XW, 2000
)
0.31
" The dosed radioactivity was excreted mostly in the feces via the hepatobiliary route."( Disposition of TAK-044, a new endothelin antagonist, in rats and dogs.
Kondo, T; Maeshiba, Y; Takeuchi, T; Tsukuda, R; Yamashita, K; Yoshimura, Y, 2002
)
0.31
" Therefore, it may be necessary to adjust the dosage of the TAK-044 in combination with ciclosporin in the course of the first clinical trials."( Pharmacokinetic interaction between TAK-044, a new endothelin antagonist, and ciclosporin in rats.
Maeshiba, Y; Tsukuda, R; Yamashita, K; Yoshimura, Y, 2002
)
0.31
"The dose-response relationship of chronic noradrenaline infusion on arterial pressure was characterized to identify a dose that would produce sustained hypertension, and the effect of combined endothelin ETA and ETB receptor blockade (TAK-044) on the response to this dose was then examined."( Role of endothelin in noradrenaline-induced hypertension in rats.
Anderson, WP; Boesen, EI; Kett, MM, 2005
)
0.33
[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)
Endothelin-1 receptorHomo sapiens (human)IC50 (µMol)0.00020.00000.76479.9000AID66198
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (74)

Processvia Protein(s)Taxonomy
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 (3)

Processvia Protein(s)Taxonomy
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 (1)

Processvia Protein(s)Taxonomy
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 (4)

Assay IDTitleYearJournalArticle
AID66214Selectivity for endothelin A receptor over endothelin receptor B2004Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8
Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID66198Displacement of [125I]ET-1 from Endothelin A receptor2004Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8
Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID12758Compound was evaluated for oral bioavailability in rats; peptide2004Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8
Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID12106Half life period was evaluated in rat; 0.5-1.02004Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8
Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (98)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's43 (43.88)18.2507
2000's53 (54.08)29.6817
2010's2 (2.04)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: 9.39

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

MetricThis Compound (vs All)
Research Demand Index9.39 (24.57)
Research Supply Index4.74 (2.92)
Research Growth Index4.13 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (9.39)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials8 (7.62%)5.53%
Reviews7 (6.67%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other90 (85.71%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]