Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7JYSK9)

DOT Name C-C motif chemokine 18 (CCL18)
Synonyms
Alternative macrophage activation-associated CC chemokine 1; AMAC-1; CC chemokine PARC; Dendritic cell chemokine 1; DC-CK1; Macrophage inflammatory protein 4; MIP-4; Pulmonary and activation-regulated chemokine; Small-inducible cytokine A18
Gene Name CCL18
Related Disease
Endometrial cancer ( )
Endometrial carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Advanced cancer ( )
Allergic asthma ( )
Arteriosclerosis ( )
Asthma ( )
Atherosclerosis ( )
Atopic dermatitis ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Clear cell renal carcinoma ( )
Gastric cancer ( )
Glioma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Matthew-Wood syndrome ( )
Metastatic malignant neoplasm ( )
Nasal polyp ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Pulmonary fibrosis ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
Sjogren syndrome ( )
Skin disease ( )
Stomach cancer ( )
Systemic sclerosis ( )
Urinary tract infection ( )
Bullous pemphigoid ( )
Chronic obstructive pulmonary disease ( )
Colon cancer ( )
Colon carcinoma ( )
Early-onset anterior polar cataract ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
IgG4 related disease ( )
Neuroblastoma ( )
Melanoma ( )
Pneumonitis ( )
Pulmonary disease ( )
Glioblastoma multiforme ( )
UniProt ID
CCL18_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4MHE
Pfam ID
PF00048
Sequence
MKGLAAALLVLVCTMALCSCAQVGTNKELCCLVYTSWQIPQKFIVDYSETSPQCPKPGVI
LLTKRGRQICADPNKKWVQKYISDLKLNA
Function
Chemotactic factor that attracts lymphocytes but not monocytes or granulocytes. May be involved in B-cell migration into B-cell follicles in lymph nodes. Attracts naive T-lymphocytes toward dendritic cells and activated macrophages in lymph nodes, has chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus may play a role in both humoral and cell-mediated immunity responses.
Tissue Specificity
Expressed at high levels in lung, lymph nodes, placenta, bone marrow, dendritic cells present in germinal centers and T-cell areas of secondary lymphoid organs and macrophages derived from peripheral blood monocytes. Not expressed by peripheral blood monocytes and a monocyte-to-macrophage differentiation is a prerequisite for expression. Expressed in synovial fluids from patients with rheumatoid and septic arthritis and in ovarian carcinoma ascitic fluid.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
Chemokine sig.ling pathway (hsa04062 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Endometrial cancer DISW0LMR Definitive Altered Expression [1]
Endometrial carcinoma DISXR5CY Definitive Altered Expression [1]
Prostate cancer DISF190Y Definitive Altered Expression [2]
Prostate carcinoma DISMJPLE Definitive Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Allergic asthma DISHF0H3 Strong Biomarker [4]
Arteriosclerosis DISK5QGC Strong Altered Expression [5]
Asthma DISW9QNS Strong Altered Expression [4]
Atherosclerosis DISMN9J3 Strong Altered Expression [5]
Atopic dermatitis DISTCP41 Strong Altered Expression [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Breast carcinoma DIS2UE88 Strong Altered Expression [7]
Breast neoplasm DISNGJLM Strong Biomarker [8]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [9]
Gastric cancer DISXGOUK Strong Altered Expression [10]
Glioma DIS5RPEH Strong Biomarker [11]
Lung cancer DISCM4YA Strong Biomarker [12]
Lung carcinoma DISTR26C Strong Biomarker [12]
Lung neoplasm DISVARNB Strong Biomarker [13]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [14]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [7]
Nasal polyp DISLP3XE Strong Altered Expression [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [12]
Obesity DIS47Y1K Strong Biomarker [16]
Osteosarcoma DISLQ7E2 Strong Biomarker [17]
Ovarian cancer DISZJHAP Strong Biomarker [18]
Ovarian neoplasm DISEAFTY Strong Biomarker [18]
Pancreatic cancer DISJC981 Strong Biomarker [14]
Pancreatic ductal carcinoma DIS26F9Q Strong Biomarker [14]
Pulmonary fibrosis DISQKVLA Strong Altered Expression [19]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [9]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [20]
Sjogren syndrome DISUBX7H Strong Biomarker [21]
Skin disease DISDW8R6 Strong Altered Expression [22]
Stomach cancer DISKIJSX Strong Altered Expression [10]
Systemic sclerosis DISF44L6 Strong Altered Expression [19]
Urinary tract infection DISMT6UV Strong Genetic Variation [23]
Bullous pemphigoid DISOJLKV moderate Biomarker [24]
Chronic obstructive pulmonary disease DISQCIRF moderate Altered Expression [25]
Colon cancer DISVC52G moderate Altered Expression [26]
Colon carcinoma DISJYKUO moderate Altered Expression [26]
Early-onset anterior polar cataract DISTOPIY moderate Altered Expression [27]
Head-neck squamous cell carcinoma DISF7P24 moderate Altered Expression [28]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [29]
IgG4 related disease DIS1U0UF moderate Biomarker [30]
Neuroblastoma DISVZBI4 moderate Altered Expression [31]
Melanoma DIS1RRCY Disputed Posttranslational Modification [32]
Pneumonitis DIS88E0K Disputed Biomarker [33]
Pulmonary disease DIS6060I Disputed Biomarker [33]
Glioblastoma multiforme DISK8246 Limited Biomarker [34]
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⏷ Show the Full List of 50 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
Ciclosporin DMAZJFX Approved Ciclosporin increases the methylation of C-C motif chemokine 18 (CCL18). [35]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of C-C motif chemokine 18 (CCL18). [40]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of C-C motif chemokine 18 (CCL18). [36]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of C-C motif chemokine 18 (CCL18). [37]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of C-C motif chemokine 18 (CCL18). [38]
Testosterone Undecanoate DMZO10Y Approved Testosterone Undecanoate increases the expression of C-C motif chemokine 18 (CCL18). [39]
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References

1 Macrophage ER promoted invasion of endometrial cancer cell by mTOR/KIF5B-mediated epithelial to mesenchymal transition.Immunol Cell Biol. 2019 Jul;97(6):563-576. doi: 10.1111/imcb.12245. Epub 2019 Mar 14.
2 Sex steroid-induced DNA methylation changes and inflammation response in prostate cancer.Cytokine. 2016 Oct;86:110-118. doi: 10.1016/j.cyto.2016.07.006. Epub 2016 Aug 5.
3 Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+ T cell counts in HIV-1-infected Patients with a Suppressed Viral Load.Sci Rep. 2019 Apr 12;9(1):5963. doi: 10.1038/s41598-019-41588-1.
4 Segmental allergen challenge enhances chitinase activity and levels of CCL18 in mild atopic asthma.Clin Exp Allergy. 2013 Feb;43(2):187-97. doi: 10.1111/cea.12032.
5 Tumor Necrosis Factor- and C-C Motif Chemokine Ligand 18 Associate with Atherosclerotic Lipid Accumulation In situ and In vitro.Curr Pharm Des. 2018;24(24):2883-2889. doi: 10.2174/1381612824666180911120726.
6 CD1c+ Blood Dendritic Cells in Atopic Dermatitis are Premature and Can Produce Disease-specific Chemokines.Acta Derm Venereol. 2017 Mar 10;97(3):325-331. doi: 10.2340/00015555-2540.
7 Positive expression of chemokine (C-C Motif) ligand 18 and prognosis in cancer: A meta-analysis.J BUON. 2018 Jul-Aug;23(4):1185-1194.
8 Acetylation of ACAP4 regulates CCL18-elicited breast cancer cell migration and invasion.J Mol Cell Biol. 2018 Dec 1;10(6):559-572. doi: 10.1093/jmcb/mjy058.
9 The suppressing role of miR-622 in renal cell carcinoma progression by down-regulation of CCL18/MAPK signal pathway.Cell Biosci. 2018 Mar 2;8:17. doi: 10.1186/s13578-018-0212-8. eCollection 2018.
10 CCL18 promotes the invasion and migration of gastric cancer cells via ERK1/2/NF-B signaling pathway.Tumour Biol. 2016 Jan;37(1):641-51. doi: 10.1007/s13277-015-3825-0. Epub 2015 Aug 5.
11 Chemokine (C-C motif) ligand 18 is highly expressed in glioma tissues and promotes invasion of glioblastoma cells.J Cancer Res Ther. 2019;15(2):358-364. doi: 10.4103/jcrt.JCRT_360_17.
12 The serum level of CC chemokine ligand 18 correlates with the prognosis of non-small cell lung cancer.Int J Biol Markers. 2019 Jun;34(2):156-162. doi: 10.1177/1724600819829758. Epub 2019 May 3.
13 CC-chemokine ligand 18 induces epithelial to mesenchymal transition in lung cancer A549 cells and elevates the invasive potential.PLoS One. 2013;8(1):e53068. doi: 10.1371/journal.pone.0053068. Epub 2013 Jan 18.
14 Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma.Cell Death Dis. 2018 May 1;9(5):453. doi: 10.1038/s41419-018-0486-0.
15 Expression profiles of regulatory and helper T-cell-associated genes in nasal polyposis.Allergy. 2012 Jun;67(6):732-40. doi: 10.1111/j.1398-9995.2012.02811.x. Epub 2012 Mar 30.
16 Adipose and Circulating CCL18 Levels Associate With Metabolic Risk Factors in Women.J Clin Endocrinol Metab. 2016 Nov;101(11):4021-4029. doi: 10.1210/jc.2016-2390. Epub 2016 Jul 26.
17 Macrophage-derived CCL18 promotes osteosarcoma proliferation and migration by upregulating the expression of UCA1.J Mol Med (Berl). 2019 Jan;97(1):49-61. doi: 10.1007/s00109-018-1711-0. Epub 2018 Nov 13.
18 Evaluation of serum CCL18 as a potential biomarker for ovarian cancer.Cancer Biomark. 2017 Dec 12;21(1):97-104. doi: 10.3233/CBM-170305.
19 Performance of Candidate Serum Biomarkers for Systemic Sclerosis-Associated Interstitial Lung Disease.Arthritis Rheumatol. 2019 Jun;71(6):972-982. doi: 10.1002/art.40815. Epub 2019 Apr 26.
20 Arthritic and non-arthritic synovial fluids modulate IL10 and IL1RA gene expression in differentially activated primary human monocytes.Osteoarthritis Cartilage. 2015 Nov;23(11):1853-7. doi: 10.1016/j.joca.2015.06.003.
21 Pathogenesis of IgG4-related disease. Comparison with Sjgren's syndrome.Mod Rheumatol. 2020 Jan;30(1):7-16. doi: 10.1080/14397595.2019.1650694. Epub 2019 Aug 19.
22 Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis.J Eur Acad Dermatol Venereol. 2013 Jan;27(1):e60-7. doi: 10.1111/j.1468-3083.2012.04495.x. Epub 2012 Mar 9.
23 High frequency of aac(6')-Ib-cr gene associated with double mutations in gyrA and parC in Escherichia coli isolates from patients with urinary tract infections.J Glob Antimicrob Resist. 2018 Jun;13:180-183. doi: 10.1016/j.jgar.2017.12.013. Epub 2018 Jan 4.
24 Minocycline decreases Th2 chemokines from M2 macrophages: Possible mechanisms for the suppression of bullous pemphigoid by traditional bullous disease drugs.Exp Dermatol. 2018 Nov;27(11):1268-1272. doi: 10.1111/exd.13779. Epub 2018 Oct 9.
25 Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization.Int J Chron Obstruct Pulmon Dis. 2017 Jan 5;12:199-208. doi: 10.2147/COPD.S118424. eCollection 2017.
26 Surgical trauma-induced CCL18 promotes recruitment of regulatory T cells and colon cancer progression.J Cell Physiol. 2019 Apr;234(4):4608-4616. doi: 10.1002/jcp.27245. Epub 2018 Sep 14.
27 Course of SP-D, YKL-40, CCL18 and CA 15-3 in adult patients hospitalised with community-acquired pneumonia and their association with disease severity and aetiology: A post-hoc analysis.PLoS One. 2018 Jan 11;13(1):e0190575. doi: 10.1371/journal.pone.0190575. eCollection 2018.
28 CCL18 promotes the metastasis of squamous cell carcinoma of the head and neck through MTDH-NF-B signalling pathway.J Cell Mol Med. 2019 Apr;23(4):2689-2701. doi: 10.1111/jcmm.14168. Epub 2019 Feb 15.
29 CTGF secreted by mesenchymal-like hepatocellular carcinoma cells plays a role in the polarization of macrophages in hepatocellular carcinoma progression.Biomed Pharmacother. 2017 Nov;95:111-119. doi: 10.1016/j.biopha.2017.08.004. Epub 2017 Sep 12.
30 Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease.Mod Rheumatol. 2020 Jul;30(4):729-737. doi: 10.1080/14397595.2019.1632061. Epub 2019 Aug 8.
31 The Ews/Fli-1 fusion gene changes the status of p53 in neuroblastoma tumor cell lines.Cancer Res. 2004 Oct 15;64(20):7288-95. doi: 10.1158/0008-5472.CAN-04-1610.
32 The long non-coding RNA CRNDE competed endogenously with miR-205 to promote proliferation and metastasis of melanoma cells by targeting CCL18.Cell Cycle. 2018;17(18):2296-2308. doi: 10.1080/15384101.2018.1526602. Epub 2018 Oct 9.
33 Is serum level of CC chemokine ligand 18 a biomarker for the prediction of radiation induced lung toxicity (RILT)?.PLoS One. 2017 Sep 28;12(9):e0185350. doi: 10.1371/journal.pone.0185350. eCollection 2017.
34 Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8.J Extracell Vesicles. 2018 Mar 13;7(1):1446660. doi: 10.1080/20013078.2018.1446660. eCollection 2018.
35 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
36 Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
37 Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
38 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
39 Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
40 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.