Target Information
| Target General Information | Top | |||||
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| Target ID |
T22095
(Former ID: TTDC00214)
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| Target Name |
Interleukin-17 (IL17)
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| Synonyms |
Interleukin-17A; IL-17A; IL-17; Cytotoxic T-lymphocyte-associated antigen 8; Cytotoxic T lymphocyte-associated antigen 8; CTLA8; CTLA-8
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| Gene Name |
IL17A
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Psoriasis [ICD-11: EA90] | |||||
| Function |
The heterodimer formed by IL17A and IL17F is a ligand for the heterodimeric complex formed by IL17RA and IL17RC. Involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines. Ligand for IL17RA and IL17RC.
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| BioChemical Class |
Cytokine: interleukin
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| UniProt ID | ||||||
| Sequence |
MTPGKTSLVSLLLLLSLEAIVKAGITIPRNPGCPNSEDKNFPRTVMVNLNIHNRNTNTNP
KRSSDYYNRSTSPWNLHRNEDPERYPSVIWEAKCRHLGCINADGNVDYHMNSVPIQQEIL VLRREPPHCPNSFRLEKILVSVGCTCVTPIVHHVA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T29B10 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Bimekizumab | Drug Info | Approved | Plaque psoriasis | [2] | |
| 2 | Brodalumab | Drug Info | Approved | Plaque psoriasis | [3] | |
| 3 | Ixekizumab | Drug Info | Approved | Plaque psoriasis | [4] | |
| Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
| 1 | ABT-122 | Drug Info | Phase 2 | Rheumatoid arthritis | [5], [6], [7] | |
| 2 | CJM112 | Drug Info | Phase 2 | Acne vulgaris | [8] | |
| 3 | CNTO-6785 | Drug Info | Phase 2 | Rheumatoid arthritis | [9] | |
| 4 | COVA322 | Drug Info | Phase 1/2a | Psoriasis vulgaris | [10] | |
| 5 | SHR-1314 | Drug Info | Phase 1/2 | Plaque psoriasis | [11] | |
| 6 | ABBV-257 | Drug Info | Phase 1 | Rheumatoid arthritis | [7] | |
| 7 | ALX-0761 | Drug Info | Phase 1 | Psoriasis vulgaris | [12] | |
| 8 | SCH-900117 | Drug Info | Phase 1 | Rheumatoid arthritis | [13] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | RG-4934 | Drug Info | Discontinued in Phase 1 | Arthritis | [14] | |
| 2 | RO7040547 | Drug Info | Discontinued in Phase 1 | Asthma | [15] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | Brodalumab | Drug Info | [16] | |||
| 2 | Ixekizumab | Drug Info | [1], [17] | |||
| 3 | ABT-122 | Drug Info | [18] | |||
| 4 | COVA322 | Drug Info | [22] | |||
| 5 | ALX-0761 | Drug Info | [22] | |||
| 6 | SCH-900117 | Drug Info | [23] | |||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | CJM112 | Drug Info | [7], [11], [19], [20] | |||
| 2 | SHR-1314 | Drug Info | [11] | |||
| 3 | ABBV-257 | Drug Info | [7] | |||
| 4 | RO7040547 | Drug Info | [25] | |||
| 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: (9's,17'r)-6'-Chloro-N-Methyl-9'-{[(1-Methyl-1h-Pyrazol-5-Yl)carbonyl]amino}-10',19'-Dioxo-2'-Oxa-11',18'-Diazaspiro[cyclopentane-1,21'-Tetracyclo[20.2.2.2~12,15~.1~3,7~]nonacosane]-1'(24'),3'(29'),4',6',12',14',22',25',27'-Nonaene-17'-Carboxamide | Ligand Info | |||||
| Structure Description | Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists | PDB:5HI4 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [26] |
| PDB Sequence |
RSSDYYNRST
48 SPWNLHRNED58 PERYPSVIWE68 AKCRHLGCIN78 ADGNVDYHMN88 SVPIQQEILV 98 LRREPPPNSF110 RLEKILVSVG120 CTCVTPIVH
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| Ligand Name: (5P)-2-hydroxy-5-(6-methylquinolin-5-yl)benzoic acid | Ligand Info | |||||
| Structure Description | IL17A homodimer bound to Compound 7 | PDB:8DYG | ||||
| Method | X-ray diffraction | Resolution | 1.49 Å | Mutation | Yes | [27] |
| PDB Sequence |
TVMVNPKRSS
64 DYYNRSTSPW74 NLHRNEDPER84 YPSVIWEAKC94 RHLGCINADG104 NVDYHMNSVP 114 IQQEILVLRR124 ESFRLEKILV140 SVGCTCVTPI150 VHH
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| 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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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 | ||
| IL-17 signaling pathway | hsa04657 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Th17 cell differentiation | hsa04659 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 16 | Degree centrality | 1.72E-03 | Betweenness centrality | 5.60E-04 |
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| Closeness centrality | 2.30E-01 | Radiality | 1.40E+01 | Clustering coefficient | 3.75E-01 |
| Neighborhood connectivity | 3.36E+01 | Topological coefficient | 1.13E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | Inflammatory bowel disease (IBD) | |||||
| 3 | Rheumatoid arthritis | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Interleukin signaling pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | IL27-mediated signaling events | |||||
| 2 | IL23-mediated signaling events | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| 2 | Allograft Rejection | |||||
| 3 | IL17 signaling pathway | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Brodalumab and ixekizumab, anti-interleukin-17-receptor antibodies for psoriasis: a critical appraisal. Br J Dermatol. 2012 Oct;167(4):710-3; discussion 714-5. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 761151 | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018 | |||||
| REF 4 | 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. | |||||
| REF 5 | ClinicalTrials.gov (NCT02349451) A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis Who Have an Inadequate Response to Methotrexate. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT02433340) Phase 2, Multicenter, Open-Label Extension (OLE) Study With ABT-122 in Rheumatoid Arthritis Subjects Who Have Completed the Preceding M12-963 Study | |||||
| REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | ClinicalTrials.gov (NCT02998671) Study of Efficacy and Safety of CJM112 in Patients With Moderate to Severe Inflammatory Acne. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT01909427) An Efficacy And Safety Study of CNTO 6785 In Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy. U.S. National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT02243787) Safety and Tolerability Study of COVA322 in Patients With Stable Chronic Moderate-to-severe Plaque Psoriasis | |||||
| REF 11 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 12 | ClinicalTrials.gov (NCT02156466) Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects | |||||
| 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 800029914) | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032677) | |||||
| REF 15 | ClinicalTrials.gov (NCT02748642) A Study to Investigate the Safety, Pharmacokinetics, and Immunogenicity of BITS7201A in Healthy Volunteers and Participants With Mild Atopic Asthma. U.S. National Institutes of Health. | |||||
| REF 16 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 17 | A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response totumor necrosis factor inhibitors. Arthritis Rheumatol. 2014 Jul;66(7):1693-704. | |||||
| REF 18 | DOI: 10.1136/annrheumdis-2015-eular.4042 | |||||
| REF 19 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 20 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 21 | Targeting the IL-17-T(H)17 pathway. Nat Rev Drug Discov. 2015 Jan;14(1):11-2. | |||||
| REF 22 | Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. | |||||
| REF 23 | Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012 Oct;11(10):763-76. | |||||
| REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032677) | |||||
| REF 25 | Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608. | |||||
| REF 26 | Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists. Sci Rep. 2016 Aug 16;6:30859. | |||||
| REF 27 | Identification and structure-based drug design of cell-active inhibitors of interleukin 17A at a novel C-terminal site. Sci Rep. 2022 Aug 26;12(1):14561. | |||||
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