Target Information
Target General Information | Top | |||||
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Target ID |
T06841
(Former ID: TTDI01808)
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Target Name |
Interleukin-23 (IL23)
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Synonyms |
UNQ2498/PRO5798; SGRF; P40 subunit of interleukin-23; Interleukin-23 subunit p19; Interleukin-23 subunit alpha; Interleukin 23 subunit alpha; IL-23p19; IL-23-A; IL-23 subunit alpha; IL-23
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Gene Name |
IL23A
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Psoriasis [ICD-11: EA90] | |||||
Function |
IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity.
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BioChemical Class |
Cytokine: interleukin
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UniProt ID | ||||||
Sequence |
MLGSRAVMLLLLLPWTAQGRAVPGGSSPAWTQCQQLSQKLCTLAWSAHPLVGHMDLREEG
DEETTNDVPHIQCGDGCDPQGLRDNSQFCLQRIHQGLIFYEKLLGSDIFTGEPSLLPDSP VGQLHASLLGLSQLLQPEGHHWETQQIPSLSPSQPWQRLLLRFKILRSLQAFVAVAARVF AHGAATLSP Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T51AX1 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
1 | CNTO-1959 | Drug Info | Approved | Plaque psoriasis | [2] | |
2 | Risankizumab | Drug Info | Approved | Plaque psoriasis | [3] | |
3 | Tildrakizumab | Drug Info | Approved | Plaque psoriasis | [4] | |
4 | Ustekinumab | Drug Info | Approved | Plaque psoriasis | [5], [6] | |
Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
1 | ABP 654 | Drug Info | Phase 3 | Psoriatic arthritis | [7] | |
2 | BI 655066 | Drug Info | Phase 3 | Chronic plaque psoriasis | [8] | |
3 | Brazikumab | Drug Info | Phase 3 | Crohn disease | [9] | |
4 | MK-3222 | Drug Info | Phase 3 | Psoriasis vulgaris | [10], [11] | |
5 | CNT0-1959 | Drug Info | Phase 2 | Rheumatoid arthritis | [12] | |
6 | AMG-139 | Drug Info | Phase 1 | Crohn disease | [13] | |
7 | mRNA-2752 | Drug Info | Phase 1 | Solid tumour/cancer | [14] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | Risankizumab | Drug Info | [3] | |||
2 | Brazikumab | Drug Info | [19] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Tildrakizumab | Drug Info | [4] | |||
Replacement | [+] 1 Replacement drugs | + | ||||
1 | mRNA-2752 | Drug Info | [22] |
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 | ||
C-type lectin receptor signaling pathway | hsa04625 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
JAK-STAT signaling pathway | hsa04630 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Th17 cell differentiation | hsa04659 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 8 | Degree centrality | 8.59E-04 | Betweenness centrality | 7.75E-06 |
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Closeness centrality | 2.19E-01 | Radiality | 1.38E+01 | Clustering coefficient | 6.07E-01 |
Neighborhood connectivity | 3.71E+01 | Topological coefficient | 2.13E-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 | [+] 19 KEGG Pathways | + | ||||
1 | Cytokine-cytokine receptor interaction | |||||
2 | Toll-like receptor signaling pathway | |||||
3 | RIG-I-like receptor signaling pathway | |||||
4 | Jak-STAT signaling pathway | |||||
5 | Type I diabetes mellitus | |||||
6 | Pertussis | |||||
7 | Legionellosis | |||||
8 | Leishmaniasis | |||||
9 | Chagas disease (American trypanosomiasis) | |||||
10 | African trypanosomiasis | |||||
11 | Malaria | |||||
12 | Toxoplasmosis | |||||
13 | Amoebiasis | |||||
14 | Tuberculosis | |||||
15 | Measles | |||||
16 | Influenza A | |||||
17 | Herpes simplex infection | |||||
18 | Inflammatory bowel disease (IBD) | |||||
19 | Allograft rejection | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | Toll-like receptor signaling pathway | |||||
2 | Aryl Hydrocarbon Receptor Pathway | |||||
3 | Allograft Rejection | |||||
4 | Regulation of toll-like receptor signaling pathway |
References | Top | |||||
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REF 1 | Interleukin-23 in the pathogenesis and treatment of psoriasis. Skin Therapy Lett. 2015 Mar-Apr;20(2):1-4. | |||||
REF 2 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019 | |||||
REF 4 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
REF 5 | 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: 6885). | |||||
REF 6 | Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. | |||||
REF 7 | ClinicalTrials.gov (NCT04607980) A Phase 3, Multicenter, Randomized, Double-Blind Study Evaluating the Efficacy and Safety of ABP 654 Compared With Ustekinumab in Subjects With Moderate to Severe Plaque Psoriasis. U.S.National Institutes of Health. | |||||
REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 9 | ClinicalTrials.gov (NCT03961815) An Open-label, Long-term Extension Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (INTREPID OLE). U.S.National Institutes of Health. | |||||
REF 10 | 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: 8093). | |||||
REF 11 | ClinicalTrials.gov (NCT01936688) A Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous MK-3222 in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-012). U.S. National Institutes of Health. | |||||
REF 12 | Anti-Interleukin-23 Monoclonal Antibody Guselkumab Shows Significant Efficacy in Treatment of Moderate to Severe Plaque Psoriasis. Janssen Research & Development, LLC (Janssen). Mar 24, 2014. | |||||
REF 13 | ClinicalTrials.gov (NCT01258205) Multiple Ascending Doses of AMG 139 in Healthy and Crohn's Disease Subjects. U.S. National Institutes of Health. | |||||
REF 14 | ClinicalTrials.gov (NCT03739931) Dose Escalation Study of mRNA-2752 for Intratumoral Injection to Participants With Advanced Malignancies. U.S. National Institutes of Health. | |||||
REF 15 | Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63. | |||||
REF 16 | Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59. | |||||
REF 17 | Clinical pipeline report, company report or official report of Amgen | |||||
REF 18 | Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015 Jul;136(1):116-124.e7. | |||||
REF 19 | Blockade of IL-23: What is in the Pipeline? J Crohns Colitis. 2022 May 11;16(Supplement_2):ii64-ii72. | |||||
REF 20 | Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. | |||||
REF 21 | Preclinical development of AMG 139, a human antibody specifically targeting IL-23. Br J Pharmacol. 2015 Jan;172(1):159-72. | |||||
REF 22 | Clinical pipeline report, company report or official report of Moderna Therapeutics. |
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