Target Information
| Target General Information | Top | |||||
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| Target ID |
T98708
(Former ID: TTDI01944)
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| Target Name |
Parathyroid hormone (PTH)
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| Synonyms |
Parathyrin; Parathormone
Click to Show/Hide
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| Gene Name |
PTH
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Skeletal anomaly [ICD-11: LD24] | |||||
| Function |
Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells. PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion.
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| UniProt ID | ||||||
| Sequence |
MIPAKDMAKVMIVMLAICFLTKSDGKSVKKRSVSEIQLMHNLGKHLNSMERVEWLRKKLQ
DVHNFVALGAPLAPRDAGSQRPRKKEDNVLVESHEKSLGEADKADVNVLTKAKSQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A02136 ; BADD_A04839 | |||||
| HIT2.0 ID | T16YT9 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | KUR-111 | Drug Info | Phase 2 | Bone disease | [4] | |
| 2 | Ostabolin-C | Drug Info | Phase 2 | Osteoporosis | [5] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | ABX-PTH | Drug Info | Terminated | Parathyroid disease | [6] | |
| 2 | SUN-E3001 | Drug Info | Terminated | Osteoporosis | [7] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | KUR-111 | Drug Info | [8] | |||
| 2 | Ostabolin-C | Drug Info | [9] | |||
| 3 | SUN-E3001 | Drug Info | [11] | |||
| 4 | MG-1101 | Drug Info | [12] | |||
| 5 | parathyroid hormone | Drug Info | [12] | |||
| 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 |
|---|---|---|---|
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Parathyroid hormone synthesis, secretion and action | hsa04928 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Endocrine and other factor-regulated calcium reabsorption | hsa04961 | Affiliated Target |
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| Class: Organismal Systems => Excretory system | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 4.22E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 1.76E-01 | Radiality | 1.29E+01 | Clustering coefficient | 2.00E-01 |
| Neighborhood connectivity | 4.60E+00 | Topological coefficient | 2.44E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Class B/2 (Secretin family receptors) | |||||
| 2 | G alpha (s) signalling events | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Endochondral Ossification | |||||
| 2 | Osteoblast Signaling | |||||
| 3 | Vitamin D Receptor Pathway | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| 6 | Vitamin D Metabolism | |||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4448). | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | ClinicalTrials.gov (NCT00459641) Safety and Tolerability of I-040302 in Children and Young Adults With Solitary Bone Cysts. U.S. National Institutes of Health. | |||||
| REF 5 | Clinical pipeline report, company report or official report of nektar. | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020246) | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014905) | |||||
| REF 8 | Company report (Cytos) | |||||
| REF 9 | ZT-031, a cyclized analog of parathyroid hormone(1-31) for the potential treatment of osteoporosis. IDrugs. 2008 Nov;11(11):827-40. | |||||
| REF 10 | Focus on parathyroid carcinoma. International Journal of Surgery Volume 9, Issue 1, 2011, Pages 13-19. | |||||
| REF 11 | Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res. 2003 Mar;18(3):539-43. | |||||
| REF 12 | Daily parathyroid hormone 1-34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure.J Bone Miner Res.2012 Aug;27(8):1811-20. | |||||
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