Target Information
| Target General Information | Top | |||||
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| Target ID |
T85025
(Former ID: TTDC00136)
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| Target Name |
Interleukin 7 receptor alpha (IL7R)
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| Synonyms |
Interleukin-7 receptor subunit alpha; IL-7RA; IL-7R-alpha; IL-7R subunit alpha; IL-7R alpha chain; IL-7 receptor subunit alpha; CDw127; CD127 antigen; CD127
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| Gene Name |
IL7R
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Atopic eczema [ICD-11: EA80] | |||||
| 2 | Human immunodeficiency virus disease [ICD-11: 1C60-1C62] | |||||
| 3 | Diabetes mellitus [ICD-11: 5A10] | |||||
| 4 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
| Function |
Acts as a receptor for thymic stromal lymphopoietin (TSLP). Receptor for interleukin-7.
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| BioChemical Class |
Cytokine receptor
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| UniProt ID | ||||||
| Sequence |
MTILGTTFGMVFSLLQVVSGESGYAQNGDLEDAELDDYSFSCYSQLEVNGSQHSLTCAFE
DPDVNITNLEFEICGALVEVKCLNFRKLQEIYFIETKKFLLIGKSNICVKVGEKSLTCKK IDLTTIVKPEAPFDLSVVYREGANDFVVTFNTSHLQKKYVKVLMHDVAYRQEKDENKWTH VNLSSTKLTLLQRKLQPAAMYEIKVRSIPDHYFKGFWSEWSPSYYFRTPEINNSSGEMDP ILLTISILSFFSVALLVILACVLWKKRIKPIVWPSLPDHKKTLEHLCKKPRKNLNVSFNP ESFLDCQIHRVDDIQARDEVEGFLQDTFPQQLEESEKQRLGGDVQSPNCPSEDVVITPES FGRDSSLTCLAGNVSACDAPILSSSRSLDCRESGKNGPHVYQDLLLSLGTTNSTLPPPFS LQSGILTLNPVAQGQPILTSLGSNQEEAYVTMSSFYQNQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T50FPV | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | ADX-914 | Drug Info | Phase 2 | Atopic dermatitis | [2] | |
| 2 | CYT 99007 | Drug Info | Phase 2 | Acquired immune deficiency syndrome | [3] | |
| 3 | PF-06342674 | Drug Info | Phase 1 | Type-1 diabetes | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | ADX-914 | Drug Info | [5] | |||
| 2 | PF-06342674 | Drug Info | [6], [7] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | CYT 99007 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: alpha-L-Fucose | Ligand Info | |||||
| Structure Description | Crystal structure of the unliganded human interleukin-7 receptor extracellular domain | PDB:3UP1 | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [8] |
| PDB Sequence |
DAELDDYSFS
21 CYSQLEVNGS31 QHSLTCAFED41 PDVNTTNLEF51 EICGALVEVK61 CLNFRKLQEI 71 YFIETKKFLL81 IGKSNICVKV91 GEKSLTCKKI101 DLTTIVKPEA111 PFDLSVVYRE 121 GANDFVVTFN131 TSHLQKKYVK141 VLMHDVAYRQ151 EKDENKWTHV161 NLSSTKLTLL 171 QRKLQPAAMY181 EIKVRSIPDH191 YFKGFWSEWS201 PSYYFRTPEI211 N |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Prolactin receptor (PRLR) | 24.573 (72/293) | 2.20E-08 | |
| Interleukin 21 receptor (IL21R) | 23.485 (31/132) | 5.99E-06 | |
| 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 | ||
| FoxO signaling pathway | hsa04068 | 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 | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 7.90E-05 |
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| Closeness centrality | 1.93E-01 | Radiality | 1.33E+01 | Clustering coefficient | 2.67E-01 |
| Neighborhood connectivity | 1.68E+01 | Topological coefficient | 2.59E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 6 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | FoxO signaling pathway | |||||
| 3 | PI3K-Akt signaling pathway | |||||
| 4 | Jak-STAT signaling pathway | |||||
| 5 | Hematopoietic cell lineage | |||||
| 6 | Primary immunodeficiency | |||||
| NetPath Pathway | [+] 5 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| 2 | IL2 Signaling Pathway | |||||
| 3 | IL4 Signaling Pathway | |||||
| 4 | TNFalpha Signaling Pathway | |||||
| 5 | Leptin Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Interleukin-7 signaling | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Apoptosis-related network due to altered Notch3 in ovarian cancer | |||||
| 2 | Interleukin-7 signaling | |||||
| 3 | TSLP Signaling Pathway | |||||
| 4 | IL-7 Signaling Pathway | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Perspectives on interleukin-7 therapy in HIV infection. Curr Opin HIV AIDS. 2007 May;2(3):228-33. | |||||
| REF 2 | ClinicalTrials.gov (NCT05509023) A Randomized, Double-Blind, Placebo-Controlled Phase 2a Proof-of-Concept Study Evaluating the Safety and Efficacy of ADX-914 in Subjects With Moderate to Severe Atopic Dermatitis. U.S.National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT01339000) Improving the Immune System With Human IL-7 Vaccine in Older Subjects Who Have Had Chemotherapy. U.S. National Institutes of Health. | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037233) | |||||
| REF 5 | Clinical pipeline report, company report or official report of Q32bio | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | Structural reorganization of the interleukin-7 signaling complex. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2503-8. | |||||
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