Target Information
Target General Information | Top | |||||
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Target ID |
T18872
(Former ID: TTDR01010)
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Target Name |
Metastasis-suppressor KiSS-1 (KISS1)
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Synonyms |
KiSS-1; KISS1
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Gene Name |
KISS1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Prostate cancer [ICD-11: 2C82] | |||||
Function |
Metastasis suppressor protein in malignant melanomas and in some breast cancers. May regulate events downstream of cell- matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-terminally amidated peptide, metastin which functions as the endogenous ligand of the G-protein coupled receptor GPR54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. Kp-10 is a decapeptide derived from the primary translation product, isolated in conditioned medium of first trimester trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca(2+) levels in isolated first trimester trophoblasts. Kp-10 is a paracrine/endocrine regulator in fine- tuning trophoblast invasion generated by the trophoblast itself. The receptor is also essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood.
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UniProt ID | ||||||
Sequence |
MNSLVSWQLLLFLCATHFGEPLEKVASVGNSRPTGQQLESLGLLAPGEQSLPCTERKPAA
TARLSRRGTSLSPPPESSGSPQQPGLSAPHSRQIPAPQGAVLVQREKDLPNYNWNSFGLR FGKREAAPGNHGRSAGRG Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T63VZZ |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | TAK-448 | Drug Info | Phase 2 | Prostate cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | TAK-448 | Drug Info | [1], [3] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
GnRH secretion | hsa04929 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy |
Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 8.60E-05 |
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Closeness centrality | 1.56E-01 | Radiality | 1.22E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 2.67E+00 | Topological coefficient | 3.33E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Co-Targets | Top | |||||
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Co-Targets |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
References | Top | |||||
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REF 1 | Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide.Eur J Pharmacol.2014 Jul 15;735:77-85. | |||||
REF 2 | ClinicalTrials.gov (NCT02381288) Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone. U.S. National Institutes of Health. | |||||
REF 3 | Sustained exposure to the investigational Kisspeptin analog, TAK-448, down-regulates testosterone into the castration range in healthy males and in patients with prostate cancer: results from two phase 1 studies.J Clin Endocrinol Metab.2014 Aug;99(8):E1445-53. |
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