Target Information
| Target General Information | Top | |||||
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| Target ID |
T06671
(Former ID: TTDC00221)
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| Target Name |
Interleukin-18 (IL18)
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| Synonyms |
Interleukin-1 gamma; Interferon-gamma inducing factor; Interferon gamma-inducing factor; Iboctadekin; IL1F4; IL-18; IL-1 gamma; IGIF; IFN-gamma-inducing factor
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| Gene Name |
IL18
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Adaptive immunity immunodeficiency [ICD-11: 4A01] | |||||
| Function |
Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells. A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses.
Click to Show/Hide
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| BioChemical Class |
Cytokine: interleukin
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| UniProt ID | ||||||
| Sequence |
MAAEPVEDNCINFVAMKFIDNTLYFIAEDDENLESDYFGKLESKLSVIRNLNDQVLFIDQ
GNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAVTISVKCEKISTLSCENKIISFK EMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLACEKERDLFKLILKKEDEL GDRSIMFTVQNED Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T63EMC | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | Tadekinig alfa | Drug Info | Phase 3 | XIAP deficiency | [2] | |
| 2 | GSK-1070806 | Drug Info | Phase 2 | Type-2 diabetes | [3] | |
| 3 | Iboctadekin | Drug Info | Phase 1 | Ovarian cancer | [4] | |
| 4 | Iboctadekin + Doxil | Drug Info | Phase 1 | Ovarian cancer | [5], [6] | |
| 5 | Iboctadekin + rituximab | Drug Info | Phase 1 | Follicular lymphoma | [7] | |
| 6 | MEDI-2338 | Drug Info | Phase 1 | Chronic obstructive pulmonary disease | [8] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | IL-18BP | Drug Info | Discontinued in Phase 1 | Rheumatoid arthritis | [9] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Tadekinig alfa | Drug Info | [10] | |||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | Iboctadekin | Drug Info | [11] | |||
| 2 | Iboctadekin + Doxil | Drug Info | [12] | |||
| 3 | Iboctadekin + rituximab | Drug Info | [12] | |||
| 4 | MEDI-2338 | Drug Info | [13] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | IL-18BP | Drug Info | [14] | |||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 11 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | NOD-like receptor signaling pathway | |||||
| 3 | Cytosolic DNA-sensing pathway | |||||
| 4 | Salmonella infection | |||||
| 5 | Legionellosis | |||||
| 6 | African trypanosomiasis | |||||
| 7 | Malaria | |||||
| 8 | Tuberculosis | |||||
| 9 | Influenza A | |||||
| 10 | Inflammatory bowel disease (IBD) | |||||
| 11 | Rheumatoid arthritis | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL4 Signaling Pathway | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Interleukin signaling pathway | |||||
| 2 | Toll receptor signaling pathway | |||||
| PID Pathway | [+] 5 PID Pathways | + | ||||
| 1 | IL27-mediated signaling events | |||||
| 2 | IL12-mediated signaling events | |||||
| 3 | IL23-mediated signaling events | |||||
| 4 | Cellular roles of Anthrax toxin | |||||
| 5 | IL12 signaling mediated by STAT4 | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Interleukin-1 processing | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Hypertrophy Model | |||||
| 2 | IL1 and megakaryotyces in obesity | |||||
| 3 | Corticotropin-releasing hormone | |||||
| 4 | NOD pathway | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Targeting the IL-1 family members in skin inflammation. Curr Opin Investig Drugs. 2010 November; 11(11): 1211-1220. | |||||
| REF 2 | ClinicalTrials.gov (NCT03512314) Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT01648153) Investigate the Efficacy and Safety of GSK1070806 in Obese Subjects With T2DM. 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 800008435) | |||||
| REF 5 | Clinical pipeline report, company report or official report of GlaxoSmithKline. | |||||
| REF 6 | ClinicalTrials.gov (NCT00659178) Combination Study Of SB-485232 (Interleukin 18) And Doxil For Advanced Stage Epithelial Ovarian Cancer. U.S. National Institutes of Health. | |||||
| REF 7 | J Clin Oncol 27:15s, 2009 (suppl, abstr 8566). | |||||
| REF 8 | ClinicalTrials.gov (NCT01322594) A Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease. U.S. National Institutes of Health. | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013227) | |||||
| REF 10 | Clinical pipeline report, company report or official report of AB2 Bio. | |||||
| REF 11 | Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study. Cancer Immunol Res. 2013 Sep;1(3):168-78. | |||||
| REF 12 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | |||||
| REF 13 | Cytokine inhibition in the treatment of COPD. Int J Chron Obstruct Pulmon Dis. 2014; 9: 397-412. | |||||
| REF 14 | Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96. | |||||
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