Target Information
Target General Information | Top | |||||
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Target ID |
T22995
(Former ID: TTDI02090)
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Target Name |
Hepcidin (HAMP)
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Synonyms |
Putative liver tumor regressor; PLTR; Liverexpressed antimicrobial peptide 1; LEAP1; Hepcidin20; Hepc25; Hepc20; HAMP
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Gene Name |
HAMP
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 4 Target-related Diseases | + | ||||
1 | Mineral absorption/transport disorder [ICD-11: 5C64] | |||||
2 | Myeloproliferative neoplasm [ICD-11: 2A20] | |||||
3 | Thalassaemia [ICD-11: 3A50] | |||||
4 | Anemia [ICD-11: 3A00-3A9Z] | |||||
Function |
Has strong antimicrobial activity against E.coli ML35P N.cinereaand weaker against S.epidermidis, S.aureus and group b streptococcus bacteria. Active against the fungus C.albicans. No activity against P.aeruginosa (PubMed:11113131, PubMed:11034317).
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BioChemical Class |
Hepcidin family
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UniProt ID | ||||||
Sequence |
MALSSQIWAACLLLLLLLASLTSGSVFPQQTGQLAELQPQDRAGARASWMPMFQRRRRRD
THFPICIFCCGCCHRSKCGMCCKT Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T21CMG |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
1 | LJPC-401 | Drug Info | Phase 2 | Hemochromatosis | [2] | |
2 | NOX-H94 | Drug Info | Phase 2 | Anemia | [1] | |
3 | PTG-300 | Drug Info | Phase 2 | Hemochromatosis | [3] | |
4 | Hepcidin mab | Drug Info | Phase 1 | Anemia | [4] | |
5 | LY2787106 | Drug Info | Phase 1 | Anemia | [5] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | 12B9m | Drug Info | Preclinical | Anaemia | [6] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Agonist | [+] 1 Agonist drugs | + | ||||
1 | LJPC-401 | Drug Info | [2] | |||
Inhibitor | [+] 3 Inhibitor drugs | + | ||||
1 | NOX-H94 | Drug Info | [1] | |||
2 | LY2787106 | Drug Info | [9] | |||
3 | 12B9m | Drug Info | [10] | |||
Replacement | [+] 1 Replacement drugs | + | ||||
1 | PTG-300 | Drug Info | [7] |
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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
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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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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TGF-beta signaling pathway | hsa04350 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy |
Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 3.86E-04 |
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Closeness centrality | 1.74E-01 | Radiality | 1.28E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 6.00E+00 | Topological coefficient | 5.00E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Iron metabolism in placenta |
References | Top | |||||
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REF 1 | The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood. 2013 Mar 21;121(12):2311-5. | |||||
REF 2 | ClinicalTrials.gov (NCT03395704) A Study of LJPC-401 for the Treatment of Iron Overload in Adult Patients With Hereditary Hemochromatosis. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT04202965) PTG-300 in Subjects With Hereditary Hemochromatosis. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT01340976) A Phase 1 Study of LY2787106 in Cancer and Anemia. U.S. National Institutes of Health. | |||||
REF 5 | ClinicalTrials.gov (NCT01340976) A Phase 1 Study of LY2787106 in Cancer and Anemia. U.S. National Institutes of Health. | |||||
REF 6 | Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017 Jun;16(6):400-423. | |||||
REF 7 | Clinical pipeline report, company report or official report of Protagonist Therapeutics. | |||||
REF 8 | The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci. 2014 March; 35(3): 155-161. | |||||
REF 9 | A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia. J Hematol Oncol. 2017 Mar 21;10(1):73. | |||||
REF 10 | Pharmacokinetics of anti-hepcidin monoclonal antibody Ab 12B9m and hepcidin in cynomolgus monkeys. AAPS J. 2010 Dec;12(4):646-57. |
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