Page last updated: 2024-11-07

cgs 26303

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Description

CGS 26303: a potent non-peptidic inhibitor of neutral endopeptidase capable of protecting atrial natriuretic peptide from enzymatic degradation; structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID132968
CHEMBL ID290698
SCHEMBL ID653011
MeSH IDM0237847

Synonyms (14)

Synonym
cgs 26303
CHEMBL290698 ,
cgs-26303
{[(s)-2-biphenyl-4-yl-1-(1h-tetrazol-5-yl)-ethylamino]-methyl}-phosphonic acid
bdbm50064106
{[(s)-2-biphenyl-4-yl-1-(2h-tetrazol-5-yl)-ethylamino]-methyl}-phosphonic acid
{[(r)-2-biphenyl-4-yl-1-(1h-tetrazol-5-yl)-ethylamino]-methyl}-phosphonic acid
{[2-biphenyl-4-yl-1-(1h-tetrazol-5-yl)-ethylamino]-methyl}-phosphonic acid(cgs 26303)
(s)-2-biphenyl-4-yl-1-(1h-tetrazol-5-yl)ethylaminomethyl phosphonic acid
phosphonic acid, (((2-(1,1'-biphenyl)-4-yl-1-(1h-tetrazol-5-yl)ethyl)amino)methyl)-, (s)-
154116-31-1
SCHEMBL653011
DTXSID40165541
cgs26303

Research Excerpts

Overview

CGS 26303 is a potent and structurally unique non-peptidic inhibitor of neutral endopeptidase (NEP) capable of protecting atrial natriuretic peptide (ANP) from enzymatic degradation.

ExcerptReferenceRelevance
"CGS 26303 is a vasopeptidase inhibitor that simultaneously inhibits endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). "( Dual ECE/NEP inhibition on cardiac and neurohumoral function during the transition from hypertrophy to heart failure in rats.
Adiarto, S; Emoto, N; Isaka, D; Jeng, AY; Masuda, S; Raharjo, SB; Yokoyama, M, 2005
)
1.77
"CGS 26303 is a potent and structurally unique non-peptidic inhibitor of neutral endopeptidase (NEP) capable of protecting atrial natriuretic peptide (ANP) from enzymatic degradation. "( Pharmacological profile of a non-peptidic dual inhibitor of neutral endopeptidase 24.11 and endothelin-converting enzyme.
De Lombaert, S; Ghai, RD; Jeng, AY; Trapani, AJ; Webb, RL, 1994
)
1.73

Treatment

Treatment with CGS 26303 inhibited the hemolysate-induced increases in the levels of ET-1 and big ET- 1 and reduced endothelial cell injury. Treatment with C GS 26303 attenuated arterial narrowing after SAH.

ExcerptReferenceRelevance
"Treatment with CGS 26303 nearly normalized these effects."( Alteration of basilar artery rho-kinase and soluble guanylyl cyclase protein expression in a rat model of cerebral vasospasm following subarachnoid hemorrhage.
Chung, CL; Kassell, NF; Kwan, AL; Lee, PY; Loh, JK; Tsai, HP; Wang, CJ; Wu, BN; Wu, SC, 2014
)
0.74
"Treatment with CGS 26303 inhibited the hemolysate-induced increases in the levels of ET-1 and big ET-1 and reduced endothelial cell injury."( Attenuation of hemolysate-induced cerebrovascular endothelial cell injury and of production of endothelin-1 and big endothelin-1 by an endothelin-converting enzyme inhibitor.
Chang, CZ; Howng, SL; Jeng, AY; Kassell, NF; Kwan, AL; Lee, KS; Lin, CL; Winardi, D,
)
0.47
"Treatment with CGS 26303 attenuated arterial narrowing after SAH."( Attenuation of experimental subarachnoid hemorrhage-induced increases in circulating intercellular adhesion molecule-1 and cerebral vasospasm by the endothelin-converting enzyme inhibitor CGS 26303.
Dumont, AS; Huang, CS; Jeng, AY; Kassell, NF; Kuo, CL; Kwan, AL; Lin, CL; Liu, CS; Su, YF; Wang, CJ; Wu, SC, 2007
)
0.87
"Treatment with CGS 26303 attenuated arterial narrowing after SAH in both the prevention and reversal protocols."( Prevention and reversal of cerebral vasospasm by an endothelin-converting enzyme inhibitor, CGS 26303, in an experimental model of subarachnoid hemorrhage.
Bavbek, M; Jeng, AY; Kassell, NF; Kwan, AL; Lappe, RW; Lee, KS; Maniara, W; Toyoda, T, 1997
)
0.86
"Treatment with CGS 26303 at 3, 10, and 30 mg/kg resulted in dose-dependent increases in the concentrations of the compound in cerebrospinal fluid samples, and the arterial narrowing after SAH was significantly attenuated in all three groups."( Attenuation of experimental subarachnoid hemorrhage-induced cerebral vasospasm by CGS 26303, an endothelin-converting enzyme inhibitor.
Bavbek, M; Jeng, AY; Kassell, NF; Kwan, AL; Lee, KS; Toyoda, T, 1998
)
0.87
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
NeprilysinRattus norvegicus (Norway rat)IC50 (µMol)0.00100.00100.17022.3000AID143636; AID147365
NeprilysinHomo sapiens (human)IC50 (µMol)0.00100.00020.54226.7000AID147365
Endothelin-converting enzyme 1Homo sapiens (human)IC50 (µMol)0.41000.01200.56782.0000AID228593; AID67199
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (39)

Processvia Protein(s)Taxonomy
kidney developmentNeprilysinHomo sapiens (human)
placenta developmentNeprilysinHomo sapiens (human)
proteolysisNeprilysinHomo sapiens (human)
peptide metabolic processNeprilysinHomo sapiens (human)
learning or memoryNeprilysinHomo sapiens (human)
substance P catabolic processNeprilysinHomo sapiens (human)
bradykinin catabolic processNeprilysinHomo sapiens (human)
sensory perception of painNeprilysinHomo sapiens (human)
protein catabolic processNeprilysinHomo sapiens (human)
lung developmentNeprilysinHomo sapiens (human)
hormone catabolic processNeprilysinHomo sapiens (human)
response to estrogenNeprilysinHomo sapiens (human)
creatinine metabolic processNeprilysinHomo sapiens (human)
amyloid-beta metabolic processNeprilysinHomo sapiens (human)
positive regulation of neurogenesisNeprilysinHomo sapiens (human)
neuropeptide processingNeprilysinHomo sapiens (human)
cellular response to cytokine stimulusNeprilysinHomo sapiens (human)
cellular response to UV-ANeprilysinHomo sapiens (human)
cellular response to UV-BNeprilysinHomo sapiens (human)
replicative senescenceNeprilysinHomo sapiens (human)
amyloid-beta clearanceNeprilysinHomo sapiens (human)
amyloid-beta clearance by cellular catabolic processNeprilysinHomo sapiens (human)
positive regulation of long-term synaptic potentiationNeprilysinHomo sapiens (human)
protein processingNeprilysinHomo sapiens (human)
positive regulation of receptor recyclingEndothelin-converting enzyme 1Homo sapiens (human)
regulation of systemic arterial blood pressure by endothelinEndothelin-converting enzyme 1Homo sapiens (human)
G protein-coupled receptor signaling pathwayEndothelin-converting enzyme 1Homo sapiens (human)
heart developmentEndothelin-converting enzyme 1Homo sapiens (human)
substance P catabolic processEndothelin-converting enzyme 1Homo sapiens (human)
bradykinin catabolic processEndothelin-converting enzyme 1Homo sapiens (human)
calcitonin catabolic processEndothelin-converting enzyme 1Homo sapiens (human)
protein processingEndothelin-converting enzyme 1Homo sapiens (human)
peptide hormone processingEndothelin-converting enzyme 1Homo sapiens (human)
regulation of vasoconstrictionEndothelin-converting enzyme 1Homo sapiens (human)
endothelin maturationEndothelin-converting enzyme 1Homo sapiens (human)
embryonic heart tube developmentEndothelin-converting enzyme 1Homo sapiens (human)
hormone catabolic processEndothelin-converting enzyme 1Homo sapiens (human)
embryonic digit morphogenesisEndothelin-converting enzyme 1Homo sapiens (human)
ear developmentEndothelin-converting enzyme 1Homo sapiens (human)
pharyngeal system developmentEndothelin-converting enzyme 1Homo sapiens (human)
axonogenesis involved in innervationEndothelin-converting enzyme 1Homo sapiens (human)
sympathetic neuron axon guidanceEndothelin-converting enzyme 1Homo sapiens (human)
semaphorin-plexin signaling pathway involved in axon guidanceEndothelin-converting enzyme 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (11)

Processvia Protein(s)Taxonomy
phosphatidylserine bindingNeprilysinHomo sapiens (human)
endopeptidase activityNeprilysinHomo sapiens (human)
metalloendopeptidase activityNeprilysinHomo sapiens (human)
protein bindingNeprilysinHomo sapiens (human)
exopeptidase activityNeprilysinHomo sapiens (human)
zinc ion bindingNeprilysinHomo sapiens (human)
peptide bindingNeprilysinHomo sapiens (human)
protein homodimerization activityNeprilysinHomo sapiens (human)
oligopeptidase activityNeprilysinHomo sapiens (human)
cardiolipin bindingNeprilysinHomo sapiens (human)
endopeptidase activityEndothelin-converting enzyme 1Homo sapiens (human)
metalloendopeptidase activityEndothelin-converting enzyme 1Homo sapiens (human)
protein bindingEndothelin-converting enzyme 1Homo sapiens (human)
zinc ion bindingEndothelin-converting enzyme 1Homo sapiens (human)
peptide hormone bindingEndothelin-converting enzyme 1Homo sapiens (human)
protein homodimerization activityEndothelin-converting enzyme 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (26)

Processvia Protein(s)Taxonomy
cytoplasmNeprilysinHomo sapiens (human)
early endosomeNeprilysinHomo sapiens (human)
trans-Golgi networkNeprilysinHomo sapiens (human)
plasma membraneNeprilysinHomo sapiens (human)
brush borderNeprilysinHomo sapiens (human)
focal adhesionNeprilysinHomo sapiens (human)
synaptic vesicleNeprilysinHomo sapiens (human)
cell surfaceNeprilysinHomo sapiens (human)
membraneNeprilysinHomo sapiens (human)
axonNeprilysinHomo sapiens (human)
dendriteNeprilysinHomo sapiens (human)
secretory granule membraneNeprilysinHomo sapiens (human)
cytoplasmic vesicleNeprilysinHomo sapiens (human)
neuronal cell bodyNeprilysinHomo sapiens (human)
neuron projection terminusNeprilysinHomo sapiens (human)
membrane raftNeprilysinHomo sapiens (human)
synapseNeprilysinHomo sapiens (human)
extracellular exosomeNeprilysinHomo sapiens (human)
presynapseNeprilysinHomo sapiens (human)
plasma membraneNeprilysinHomo sapiens (human)
lysosomal membraneEndothelin-converting enzyme 1Homo sapiens (human)
endosomeEndothelin-converting enzyme 1Homo sapiens (human)
plasma membraneEndothelin-converting enzyme 1Homo sapiens (human)
external side of plasma membraneEndothelin-converting enzyme 1Homo sapiens (human)
endosome membraneEndothelin-converting enzyme 1Homo sapiens (human)
membraneEndothelin-converting enzyme 1Homo sapiens (human)
vesicleEndothelin-converting enzyme 1Homo sapiens (human)
Weibel-Palade bodyEndothelin-converting enzyme 1Homo sapiens (human)
perinuclear region of cytoplasmEndothelin-converting enzyme 1Homo sapiens (human)
extracellular exosomeEndothelin-converting enzyme 1Homo sapiens (human)
plasma membraneEndothelin-converting enzyme 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (6)

Assay IDTitleYearJournalArticle
AID143636In vitro inhibition of rat neutral endopeptidase2000Journal of medicinal chemistry, Feb-10, Volume: 43, Issue:3
Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action.
AID147365Inhibitory activity against neutral endopeptidase (NEP).1998Journal of medicinal chemistry, Apr-23, Volume: 41, Issue:9
Design and synthesis of potent, selective inhibitors of endothelin-converting enzyme.
AID228593In Vitro inhibition of recombinant human endothelin converting enzyme-12000Journal of medicinal chemistry, Feb-10, Volume: 43, Issue:3
Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action.
AID67206Ratio of inhibitory activities against endothelin converting enzyme-1(ECE-1) and neutral endopeptidase (NEP).1998Journal of medicinal chemistry, Apr-23, Volume: 41, Issue:9
Design and synthesis of potent, selective inhibitors of endothelin-converting enzyme.
AID67199Inhibitory activity was assessed on CHO cells expressing recombinant human Endothelin-converting enzyme 1 (ECE-1).1998Journal of medicinal chemistry, Apr-23, Volume: 41, Issue:9
Design and synthesis of potent, selective inhibitors of endothelin-converting enzyme.
AID235174Selectivity ratio of IC50 NEP/IC50 ECE2000Journal of medicinal chemistry, Feb-10, Volume: 43, Issue:3
Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (32)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's11 (34.38)18.2507
2000's19 (59.38)29.6817
2010's2 (6.25)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: 10.69

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 Index10.69 (24.57)
Research Supply Index3.53 (2.92)
Research Growth Index4.21 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.69)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews3 (9.09%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other30 (90.91%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]