Target Information
| Target General Information | Top | |||||
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| Target ID |
T07958
(Former ID: TTDI01917)
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| Target Name |
Erythropoietin (EPO)
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| Synonyms |
Epoetin
Click to Show/Hide
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| Gene Name |
EPO
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Retinopathy [ICD-11: 9B71] | |||||
| 2 | Anemia [ICD-11: 3A00-3A9Z] | |||||
| Function |
Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3. Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
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| UniProt ID | ||||||
| Sequence |
MGVHECPAWLWLLLSLLSLPLGLPVLGAPPRLICDSRVLERYLLEAKEAENITTGCAEHC
SLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQL HVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKL KLYTGEACRTGDR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A06316 | |||||
| HIT2.0 ID | T10OIU | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | MK-2578 | Drug Info | Phase 2 | Anemia | [3] | |
| 2 | Erythropoietin-transfected autologous cell therapy | Drug Info | Phase 1/2 | Anemia | [4] | |
| 3 | GC-1113 | Drug Info | Phase 1 | Anemia | [5] | |
| 4 | Long-acting erythropoietin conjugate | Drug Info | Phase 1 | Anemia | [6] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | FC EPO | Drug Info | Discontinued in Phase 1 | Anemia | [7] | |
| 2 | GLY-515n | Drug Info | Terminated | Cerebrovascular ischaemia | [8] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | MK-2578 | Drug Info | [1] | |||
| 2 | FC EPO | Drug Info | [12] | |||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | Erythropoietin-transfected autologous cell therapy | Drug Info | [9] | |||
| 2 | GC-1113 | Drug Info | [10] | |||
| 3 | Long-acting erythropoietin conjugate | Drug Info | [11] | |||
| 4 | GLY-515n | Drug Info | [13] | |||
| 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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| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| HIF-1 signaling pathway | hsa04066 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| JAK-STAT signaling pathway | hsa04630 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Hematopoietic cell lineage | hsa04640 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 12 | Degree centrality | 1.29E-03 | Betweenness centrality | 1.03E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 2.34E-01 | Radiality | 1.41E+01 | Clustering coefficient | 3.48E-01 |
| Neighborhood connectivity | 4.28E+01 | Topological coefficient | 1.37E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | HIF-1 signaling pathway | |||||
| 3 | PI3K-Akt signaling pathway | |||||
| 4 | Jak-STAT signaling pathway | |||||
| 5 | Hematopoietic cell lineage | |||||
| PID Pathway | [+] 4 PID Pathways | + | ||||
| 1 | HIF-2-alpha transcription factor network | |||||
| 2 | Signaling events mediated by Stem cell factor receptor (c-Kit) | |||||
| 3 | EPO signaling pathway | |||||
| 4 | HIF-1-alpha transcription factor network | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Regulation of gene expression by Hypoxia-inducible Factor | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | EPO Receptor Signaling | |||||
| 2 | Hematopoietic Stem Cell Differentiation | |||||
| 3 | Differentiation Pathway | |||||
| 4 | Regulation of Hypoxia-inducible Factor (HIF) by Oxygen | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Merck ditches biogeneric. Nat Biotechnol. 2010 Jul;28(7):636. | |||||
| REF 2 | ClinicalTrials.gov (NCT03927690) Multiple Dose Safety and Efficacy of LKA651 in Patients With Diabetic Macular Edema. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT00968617) A Study of MK2578 in Patients With Chronic Kidney Disease Who Are Not on Dialysis (2578-002). U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00542568) Safety and Efficacy of Sustained Erythropoietin Therapy. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01363934) To Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Erythropoietin. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT01030315) A Study of HM10760A (Long-acting Erythropoietin) in Healthy Adult Caucasian and Japanese Subjects. U.S. National Institutes of Health. | |||||
| 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 800027346) | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027536) | |||||
| REF 9 | Mesenchymal stromal cells engineered to express erythropoietin induce anti-erythropoietin antibodies and anemia in allorecipients. Mol Ther. 2009 Feb;17(2):369-72. | |||||
| REF 10 | A long-acting erythropoietin fused with noncytolytic human Fc for the treatment of anemia. Arch Pharm Res. 2012 May;35(5):757-9. | |||||
| REF 11 | Company report (Pharmexcil) | |||||
| REF 12 | Detection of EPO-Fc fusion protein in human blood: screening and confirmation protocols for sports drug testing. Drug Test Anal. 2012 Nov;4(11):818-29. | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027536) | |||||
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