Target Information

Target General Information

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Target ID

T25076 (Former ID: TTDR00412)

Target Name

Endothelin-1 (EDN1)

Synonyms

Preproendothelin-1; PPET1

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Gene Name

EDN1

Target Type

Literature-reported target

[1]

Disease

[+] 1 Target-related Diseases

Dissociative neurological symptom disorder [ICD-11: 6B60]

Function

Endothelins are endothelium-derived vasoconstrictor peptides.

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BioChemical Class

Endothelin/sarafotoxin

UniProt ID

EDN1_HUMAN

Sequence

MDYLLMIFSLLFVACQGAPETAVLGAELSAVGENGGEKPTPSPPWRLRRSKRCSCSSLMD
KECVYFCHLDIIWVNTPEHVVPYGLGSPRSKRALENLLPTKATDRENRCQCASQKDKKCW
NFCQAGKELRAEDIMEKDWNNHKKGKDCSKLGKKCIYQQLVRGRKIRRSSEEHLRQTRSE
TMRNSVKSSFHDPKLKGKPSRERYVTHNRAHW

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3D Structure

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AlphaFold

ADReCS ID

BADD_A02149 ; BADD_A02564 ; BADD_A02600

HIT2.0 ID

T93VFT

Drugs and Modes of Action

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Discontinued Drug(s)

[+] 1 Discontinued Drugs

Tetramethylpyrazine

Drug Info

Discontinued in Phase 2

Neurological disorder

[2]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 1 Modulator drugs

Tetramethylpyrazine

Drug Info

[3]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
cAMP signaling pathway	hsa04024	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
HIF-1 signaling pathway	hsa04066	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Neuroactive ligand-receptor interaction	hsa04080	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Vascular smooth muscle contraction	hsa04270	Affiliated Target
Class: Organismal Systems => Circulatory system	Pathway Hierarchy
TNF signaling pathway	hsa04668	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Melanogenesis	hsa04916	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Renin secretion	hsa04924	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Relaxin signaling pathway	hsa04926	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	15	Degree centrality	1.61E-03	Betweenness centrality	2.88E-03
Closeness centrality	2.50E-01	Radiality	1.44E+01	Clustering coefficient	1.62E-01
Neighborhood connectivity	6.05E+01	Topological coefficient	9.55E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

References

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REF 1

Predictive value of biomarkers in patients with heart failure. Curr Med Chem. 2012;19(16):2534-47.

REF 2

Determination of tetramethylpyrazine in animal serum and cerebrospinal fluid by high performance liquid chromatography. Se Pu. 2000 Jan;18(1):46-8.

REF 3

Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by endothelin-1 and decreases plasma endothelin-1 levels in experimental animals. J Cardiovasc Pharmacol. 1998;31 Suppl 1:S313-6.

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