Target Information

Target General Information

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Target ID

T58920

Target Name

Thyrotropin-releasing hormone (TRH)

Synonyms

Prothyroliberin; Pro-thyrotropin-releasing hormone; Pro-TRH

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Gene Name

TRH

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Parkinsonism [ICD-11: 8A00]

Function

As a component of the hypothalamic-pituitary-thyroid axis, it controls the secretion of thyroid-stimulating hormone (TSH) and is involved in thyroid hormone synthesis regulation. It also operates as modulator of hair growth. It promotes hair-shaft elongation, prolongs the hair cycle growth phase (anagen) and antagonizes its termination (catagen) by TGFB2. It stimulates proliferation and inhibits apoptosis of hair matrix keratinocytes.

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UniProt ID

TRH_HUMAN

Sequence

MPGPWLLLALALTLNLTGVPGGRAQPEAAQQEAVTAAEHPGLDDFLRQVERLLFLRENIQ
RLQGDQGEHSASQIFQSDWLSKRQHPGKREEEEEEGVEEEEEEEGGAVGPHKRQHPGRRE
DEASWSVDVTQHKRQHPGRRSPWLAYAVPKRQHPGRRLADPKAQRSWEEEEEEEEREEDL
MPEKRQHPGKRALGGPCGPQGAYGQAGLLLGLLDDLSRSQGAEEKRQHPGRRAAWVREPL
EE

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

KPS-0373

Drug Info

Phase 3

Parkinson disease

[2]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

RX-77368

Drug Info

Discontinued in Phase 2

Dementia

[3]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 2 Modulator drugs

KPS-0373

Drug Info

[1]

RX-77368

Drug Info

[4], [5]

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	Pathway Map
Neuroactive ligand-receptor interaction	hsa04080	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.07E-04	Radiality	3.98E-03	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.00E+00	Topological coefficient	.	Eccentricity	1
Download	Click to Download the Full PPI Network of This Target

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

References

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REF 1

DOI: 10.1002/mdc3.12057

REF 2

ClinicalTrials.gov (NCT01970111) An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD). U.S. National Institutes of Health.

REF 3

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001316)

REF 4

Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF(2).Br J Pharmacol.2002 May;136(2):237-47.

REF 5

Thyrotropin releasing hormone (TRH) and a degradation stabilized analogue (RX77368) stimulate phosphoinositide turnover in cultured astrocytes in a... Neurochem Int. 1992 Apr;20(3):307-13.

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