Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW0LRYZ)

DOT Name Interleukin-18-binding protein (IL18BP)
Synonyms IL-18BP; Tadekinig-alfa
Gene Name IL18BP
Related Disease
Acne vulgaris ( )
Multiple sclerosis ( )
Acute myocardial infarction ( )
Arteriosclerosis ( )
Asthma ( )
Atherosclerosis ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Bronchopulmonary dysplasia ( )
Cardiac failure ( )
Colon carcinoma ( )
Congestive heart failure ( )
Coronary atherosclerosis ( )
Crohn disease ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Hepatitis C virus infection ( )
HIV infectious disease ( )
Idiopathic thrombocytopenic purpura ( )
Myocardial ischemia ( )
Nephritis ( )
Peripheral arterial disease ( )
Postmenopausal osteoporosis ( )
Rheumatoid arthritis ( )
Tuberculosis ( )
Type-1/2 diabetes ( )
Urticaria ( )
Viral hepatitis ( )
Advanced cancer ( )
Pancreatic cancer ( )
Pulmonary fibrosis ( )
Dilated cardiomyopathy ( )
Diverticulitis ( )
Epithelial ovarian cancer ( )
Hepatitis, fulminant viral, susceptibility to ( )
Infectious colitis ( )
Inflammatory bowel disease ( )
Lupus nephritis ( )
Neoplasm ( )
Renal fibrosis ( )
Ulcerative colitis ( )
UniProt ID
I18BP_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7AL7
Sequence
MTMRHNWTPDLSPLWVLLLCAHVVTLLVRATPVSQTTTAATASVRSTKDPCPSQPPVFPA
AKQCPALEVTWPEVEVPLNGTLSLSCVACSRFPNFSILYWLGNGSFIEHLPGRLWEGSTS
RERGSTGTQLCKALVLEQLTPALHSTNFSCVLVDPEQVVQRHVVLAQLWAGLRATLPPTQ
EALPSSHSSPQQQG
Function Isoform A binds to IL-18 and inhibits its activity. Functions as an inhibitor of the early TH1 cytokine response.
Tissue Specificity Strongly expressed in heart, lung, placenta and spleen.
Reactome Pathway
Interleukin-18 signaling (R-HSA-9012546 )
Interleukin-37 signaling (R-HSA-9008059 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acne vulgaris DISKW8PI Definitive Biomarker [1]
Multiple sclerosis DISB2WZI Definitive Altered Expression [2]
Acute myocardial infarction DISE3HTG Strong Altered Expression [3]
Arteriosclerosis DISK5QGC Strong Altered Expression [4]
Asthma DISW9QNS Strong Altered Expression [5]
Atherosclerosis DISMN9J3 Strong Altered Expression [4]
Autoimmune disease DISORMTM Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [8]
Cardiac failure DISDC067 Strong Biomarker [9]
Colon carcinoma DISJYKUO Strong Biomarker [10]
Congestive heart failure DIS32MEA Strong Biomarker [9]
Coronary atherosclerosis DISKNDYU Strong Altered Expression [3]
Crohn disease DIS2C5Q8 Strong Altered Expression [11]
Hepatitis DISXXX35 Strong Biomarker [12]
Hepatitis A virus infection DISUMFQV Strong Biomarker [12]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [13]
HIV infectious disease DISO97HC Strong Altered Expression [14]
Idiopathic thrombocytopenic purpura DISFKGJU Strong Altered Expression [15]
Myocardial ischemia DISFTVXF Strong Altered Expression [3]
Nephritis DISQZQ70 Strong Biomarker [16]
Peripheral arterial disease DIS78WFB Strong Altered Expression [17]
Postmenopausal osteoporosis DISS0RQZ Strong Biomarker [6]
Rheumatoid arthritis DISTSB4J Strong Biomarker [6]
Tuberculosis DIS2YIMD Strong Biomarker [18]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [19]
Urticaria DIS9WQAI Strong Altered Expression [20]
Viral hepatitis DISVT5Q7 Strong Biomarker [12]
Advanced cancer DISAT1Z9 moderate Genetic Variation [21]
Pancreatic cancer DISJC981 moderate Biomarker [22]
Pulmonary fibrosis DISQKVLA moderate Biomarker [23]
Dilated cardiomyopathy DISX608J Limited Biomarker [24]
Diverticulitis DIS1AK7Q Limited Altered Expression [11]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [25]
Hepatitis, fulminant viral, susceptibility to DISURJZE Limited Unknown [12]
Infectious colitis DISKN090 Limited Altered Expression [11]
Inflammatory bowel disease DISGN23E Limited Altered Expression [11]
Lupus nephritis DISCVGPZ Limited Altered Expression [26]
Neoplasm DISZKGEW Limited Biomarker [22]
Renal fibrosis DISMHI3I Limited Genetic Variation [27]
Ulcerative colitis DIS8K27O Limited Altered Expression [11]
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⏷ Show the Full List of 42 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Interleukin-18-binding protein (IL18BP). [28]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Interleukin-18-binding protein (IL18BP). [31]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Interleukin-18-binding protein (IL18BP). [29]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Interleukin-18-binding protein (IL18BP). [30]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Interleukin-18-binding protein (IL18BP). [32]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Interleukin-18-binding protein (IL18BP). [33]
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References

1 IL-18-binding protein protects against lipopolysaccharide- induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice.J Immunol. 2001 Nov 15;167(10):5913-20. doi: 10.4049/jimmunol.167.10.5913.
2 Inflammation in the central nervous system and Th17 responses are inhibited by IFN-gamma-Induced IL-18 binding protein.J Immunol. 2010 Aug 15;185(4):2458-66. doi: 10.4049/jimmunol.0902153. Epub 2010 Jul 19.
3 IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction.Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17499-504. doi: 10.1073/pnas.0908924106. Epub 2009 Sep 25.
4 Cloning and characterization of rhesus IL-18 binding protein, a natural antagonist to IL-18.Cytokine. 2010 Sep;51(3):232-9. doi: 10.1016/j.cyto.2010.05.010.
5 Role of IL-18 in atopic asthma is determined by balance of IL-18/IL-18BP/IL-18R.J Cell Mol Med. 2018 Jan;22(1):354-373. doi: 10.1111/jcmm.13323. Epub 2017 Sep 18.
6 IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation.Sci Rep. 2016 Sep 21;6:33680. doi: 10.1038/srep33680.
7 Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer.Front Immunol. 2018 Jan 16;8:1994. doi: 10.3389/fimmu.2017.01994. eCollection 2017.
8 Bipolar disorder moderates associations between linoleic acid and markers of inflammation.J Psychiatr Res. 2017 Feb;85:29-36. doi: 10.1016/j.jpsychires.2016.10.021. Epub 2016 Oct 27.
9 Interleukin-18 mediates interleukin-1-induced cardiac dysfunction.Am J Physiol Heart Circ Physiol. 2014 Apr 1;306(7):H1025-31. doi: 10.1152/ajpheart.00795.2013. Epub 2014 Feb 14.
10 Interferon-gamma mediates gene expression of IL-18 binding protein in nonleukocytic cells.Biochem Biophys Res Commun. 2000 Jan 27;267(3):960-3. doi: 10.1006/bbrc.1999.2064.
11 Interleukin-18 is increased only in a minority of patients with active Crohn's disease.Int J Colorectal Dis. 2007 Sep;22(9):1013-20. doi: 10.1007/s00384-007-0282-2. Epub 2007 Feb 21.
12 Inherited IL-18BP deficiency in human fulminant viral hepatitis. J Exp Med. 2019 Aug 5;216(8):1777-1790. doi: 10.1084/jem.20190669. Epub 2019 Jun 18.
13 Interferon-alpha induces interleukin-18 binding protein in chronic hepatitis C patients.Clin Exp Immunol. 2002 Aug;129(2):332-8. doi: 10.1046/j.1365-2249.2002.01911.x.
14 HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation.PLoS One. 2018 Mar 30;13(3):e0194185. doi: 10.1371/journal.pone.0194185. eCollection 2018.
15 Detection of expression of IL-18 and its binding protein in Egyptian pediatric immune thrombocytopenic purpura.Platelets. 2014;25(3):193-6. doi: 10.3109/09537104.2013.784734. Epub 2013 Apr 4.
16 IL-1 family cytokines and soluble receptors in systemic lupus erythematosus.Arthritis Res Ther. 2018 Feb 8;20(1):27. doi: 10.1186/s13075-018-1525-z.
17 Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study.Heart Vessels. 2016 Jun;31(6):976-84. doi: 10.1007/s00380-015-0753-2. Epub 2015 Oct 5.
18 IL-18/IL-37/IP-10 signalling complex as a potential biomarker for discriminating active and latent TB.PLoS One. 2019 Dec 10;14(12):e0225556. doi: 10.1371/journal.pone.0225556. eCollection 2019.
19 Diabetes alters immune response patterns to acute melioidosis in humans.Eur J Immunol. 2019 Jul;49(7):1092-1106. doi: 10.1002/eji.201848037. Epub 2019 May 8.
20 Level of interleukin-18 binding protein is significantly different in patients with anaphylaxis than urticaria.Asian Pac J Allergy Immunol. 2022 Dec;40(4):368-373. doi: 10.12932/AP-270619-0588.
21 Identification of small molecule inhibitors of Interleukin-18.Sci Rep. 2017 Mar 28;7(1):483. doi: 10.1038/s41598-017-00532-x.
22 Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18 promote immune tolerance via the PD-1/PD-L1 pathway.Oncotarget. 2017 Dec 7;9(19):14803-14814. doi: 10.18632/oncotarget.22976. eCollection 2018 Mar 13.
23 Interleukin-18 promotes fibroblast senescence in pulmonary fibrosis through down-regulating Klotho expression.Biomed Pharmacother. 2019 May;113:108756. doi: 10.1016/j.biopha.2019.108756. Epub 2019 Mar 11.
24 Evidence for altered interleukin 18 (IL)-18 pathway in human heart failure.FASEB J. 2004 Nov;18(14):1752-4. doi: 10.1096/fj.04-2426fje. Epub 2004 Sep 15.
25 The IL-18 antagonist IL-18-binding protein is produced in the human ovarian cancer microenvironment.Clin Cancer Res. 2013 Sep 1;19(17):4611-20. doi: 10.1158/1078-0432.CCR-13-0568. Epub 2013 Jul 19.
26 Expressions of IL-18 and its binding protein in peripheral blood leukocytes and kidney tissues of lupus nephritis patients.Clin Rheumatol. 2010 Jul;29(7):717-21. doi: 10.1007/s10067-010-1386-6. Epub 2010 Feb 8.
27 Neutralization of IL-18 by IL-18 binding protein ameliorates bleomycin-induced pulmonary fibrosis via inhibition of epithelial-mesenchymal transition.Biochem Biophys Res Commun. 2019 Jan 8;508(2):660-666. doi: 10.1016/j.bbrc.2018.11.129. Epub 2018 Dec 4.
28 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
29 Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
30 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
31 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
32 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
33 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.