Target Information
| Target General Information | Top | |||||
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| Target ID |
T78585
(Former ID: TTDR00088)
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| Target Name |
Interleukin-5 (IL5)
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| Synonyms |
TRF protein; T-cell replacing factor; IL-5; Eosinophil differentiation factor; B-cell differentiation factor I; B cell differentiation factor I
Click to Show/Hide
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| Gene Name |
IL5
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Asthma [ICD-11: CA23] | |||||
| Function |
Factor that induces terminal differentiation of late-developing B-cells to immunoglobulin secreting cells.
Click to Show/Hide
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| BioChemical Class |
Cytokine: interleukin
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| UniProt ID | ||||||
| Sequence |
MRMLLHLSLLALGAAYVYAIPTEIPTSALVKETLALLSTHRTLLIANETLRIPVPVHKNH
QLCTEEIFQGIGTLESQTVQGGTVERLFKNLSLIKKYIDGQKKKCGEERRRVNQFLDYLQ EFLGVMNTEWIIES Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05204 | |||||
| HIT2.0 ID | T12WTT | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Benralizumab | Drug Info | Approved | Asthma | [2] | |
| 2 | Mepolizumab | Drug Info | Approved | Severe asthma | [3], [4] | |
| 3 | Reslizumab | Drug Info | Approved | Severe asthma | [5] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | Benralizumab | Drug Info | [1] | |||
| 2 | Mepolizumab | Drug Info | [8] | |||
| 3 | Reslizumab | Drug Info | [9] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | SOPHORICOSIDE | Drug Info | [10] | |||
| 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 |
|---|---|---|---|
| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | 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 | ||
| IL-17 signaling pathway | hsa04657 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Th1 and Th2 cell differentiation | hsa04658 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| T cell receptor signaling pathway | hsa04660 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Fc epsilon RI signaling pathway | hsa04664 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Intestinal immune network for IgA production | hsa04672 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 8 | Degree centrality | 8.59E-04 | Betweenness centrality | 2.55E-05 |
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| Closeness centrality | 2.12E-01 | Radiality | 1.37E+01 | Clustering coefficient | 2.50E-01 |
| Neighborhood connectivity | 2.50E+01 | Topological coefficient | 2.17E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Benralizumab a humanized mAb to IL-5R with enhanced antibody-dependent cell-mediated cytotoxicity a novel approach for the treatment of asthma | |||||
| REF 2 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
| REF 3 | 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: 7685). | |||||
| REF 4 | Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53. | |||||
| REF 5 | 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. | |||||
| REF 6 | ClinicalTrials.gov (NCT05243680) A Multi-centre, Single Arm, Open-label Extension Study to Evaluate the Long-term Safety of GSK3511294 (Depemokimab) in Adult and Adolescent Participants With Severe Asthma With an Eosinophilic Phenotype From Studies 206713 or 213744. U.S.National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT04719832) A 52-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of GSK3511294 Adjunctive Therapy in Adult and Adolescent Participants With Severe Uncontrolled Asthma With an Eosinophilic Phenotype. U.S.National Institutes of Health. | |||||
| REF 8 | Mepolizumab: 240563, anti-IL-5 monoclonal antibody - GlaxoSmithKline, anti-interleukin-5 monoclonal antibody - GlaxoSmithKline, SB 240563. Drugs R D. 2008;9(2):125-30. | |||||
| REF 9 | The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72. | |||||
| REF 10 | Design and synthesis of novel hydroxyalkylaminomethylchromones for their IL-5 inhibitory activity. Bioorg Med Chem. 2010 Jul 1;18(13):4625-9. | |||||
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