Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCTWYN8)

DOT Name C-C motif chemokine 8 (CCL8)
Synonyms HC14; Monocyte chemoattractant protein 2; Monocyte chemotactic protein 2; MCP-2; Small-inducible cytokine A8
Gene Name CCL8
Related Disease
Abdominal aortic aneurysm ( )
Adult glioblastoma ( )
Advanced cancer ( )
Allergy ( )
Alzheimer disease ( )
Classic Hodgkin lymphoma ( )
Crohn disease ( )
Cytomegalovirus infection ( )
Diabetic retinopathy ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Glioblastoma multiforme ( )
Glioma ( )
Graft-versus-host disease ( )
Hepatitis B virus infection ( )
Hereditary hemochromatosis ( )
Influenza ( )
Matthew-Wood syndrome ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoarthritis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Pneumonia ( )
Pneumonitis ( )
Sarcoidosis ( )
Squamous cell carcinoma ( )
Synovitis ( )
Tenosynovitis ( )
Ulcerative colitis ( )
Breast cancer ( )
Breast carcinoma ( )
Melanoma ( )
Plasma cell myeloma ( )
Rheumatoid arthritis ( )
Asthma ( )
Arteriosclerosis ( )
Arthritis ( )
Atherosclerosis ( )
Atopic dermatitis ( )
Chronic pancreatitis ( )
Colitis ( )
Cutaneous squamous cell carcinoma ( )
Encephalitis ( )
Hepatitis C virus infection ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Tuberculosis ( )
UniProt ID
CCL8_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1ESR; 7S59; 7S5A
Pfam ID
PF00048
Sequence
MKVSAALLCLLLMAATFSPQGLAQPDSVSIPITCCFNVINRKIPIQRLESYTRITNIQCP
KEAVIFKTKRGKEVCADPKERWVRDSMKHLDQIFQNLKP
Function
Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils. May play a role in neoplasia and inflammatory host responses. This protein can bind heparin. The processed form MCP-2(6-76) does not show monocyte chemotactic activity, but inhibits the chemotactic effect most predominantly of CCL7, and also of CCL2 and CCL5 and CCL8.
Tissue Specificity
Highest expression found in the small intestine and peripheral blood cells. Intermediate levels seen in the heart, placenta, lung, skeletal muscle, thymus, colon, ovary, spinal cord and pancreas. Low levels seen in the brain, liver, spleen and prostate.
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

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Abdominal aortic aneurysm DISD06OF Strong Altered Expression [1]
Adult glioblastoma DISVP4LU Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Allergy DIS48ZAP Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Genetic Variation [5]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [6]
Crohn disease DIS2C5Q8 Strong Altered Expression [7]
Cytomegalovirus infection DISCEMGC Strong Biomarker [8]
Diabetic retinopathy DISHGUJM Strong Biomarker [9]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [11]
Glioblastoma multiforme DISK8246 Strong Biomarker [2]
Glioma DIS5RPEH Strong Biomarker [2]
Graft-versus-host disease DIS0QADF Strong Biomarker [12]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [13]
Hereditary hemochromatosis DISVG5MT Strong Biomarker [14]
Influenza DIS3PNU3 Strong Biomarker [15]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [17]
Obesity DIS47Y1K Strong Altered Expression [18]
Osteoarthritis DIS05URM Strong Biomarker [14]
Ovarian cancer DISZJHAP Strong Altered Expression [10]
Ovarian neoplasm DISEAFTY Strong Altered Expression [10]
Pancreatic cancer DISJC981 Strong Biomarker [16]
Pneumonia DIS8EF3M Strong Biomarker [19]
Pneumonitis DIS88E0K Strong Biomarker [19]
Sarcoidosis DISE5B8Z Strong Altered Expression [20]
Squamous cell carcinoma DISQVIFL Strong Genetic Variation [17]
Synovitis DISW2GPY Strong Biomarker [21]
Tenosynovitis DISR5H9R Strong Biomarker [21]
Ulcerative colitis DIS8K27O Strong Biomarker [22]
Breast cancer DIS7DPX1 moderate Biomarker [23]
Breast carcinoma DIS2UE88 moderate Biomarker [23]
Melanoma DIS1RRCY moderate Altered Expression [24]
Plasma cell myeloma DIS0DFZ0 moderate Altered Expression [25]
Rheumatoid arthritis DISTSB4J moderate Genetic Variation [26]
Asthma DISW9QNS Disputed Altered Expression [27]
Arteriosclerosis DISK5QGC Limited Biomarker [28]
Arthritis DIST1YEL Limited Biomarker [29]
Atherosclerosis DISMN9J3 Limited Biomarker [28]
Atopic dermatitis DISTCP41 Limited Biomarker [30]
Chronic pancreatitis DISBUOMJ Limited Biomarker [31]
Colitis DISAF7DD Limited Altered Expression [32]
Cutaneous squamous cell carcinoma DIS3LXUG Limited Biomarker [33]
Encephalitis DISLD1RL Limited Altered Expression [34]
Hepatitis C virus infection DISQ0M8R Limited Altered Expression [35]
Neoplasm DISZKGEW Limited Biomarker [23]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [28]
Tuberculosis DIS2YIMD Limited Biomarker [36]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of C-C motif chemokine 8 (CCL8). [37]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of C-C motif chemokine 8 (CCL8). [38]
Testosterone DM7HUNW Approved Testosterone increases the expression of C-C motif chemokine 8 (CCL8). [38]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of C-C motif chemokine 8 (CCL8). [39]
Marinol DM70IK5 Approved Marinol increases the expression of C-C motif chemokine 8 (CCL8). [40]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of C-C motif chemokine 8 (CCL8). [41]
Bortezomib DMNO38U Approved Bortezomib affects the expression of C-C motif chemokine 8 (CCL8). [25]
Mifepristone DMGZQEF Approved Mifepristone decreases the expression of C-C motif chemokine 8 (CCL8). [43]
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⏷ Show the Full List of 8 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Morphine DMRMS0L Approved Morphine increases the secretion of C-C motif chemokine 8 (CCL8). [44]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of C-C motif chemokine 8 (CCL8). [45]
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References

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2 CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling.Lab Invest. 2020 Apr;100(4):619-629. doi: 10.1038/s41374-019-0345-3. Epub 2019 Nov 20.
3 Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.Cancer Lett. 2018 Apr 1;418:204-210. doi: 10.1016/j.canlet.2018.01.037. Epub 2018 Jan 13.
4 Expansion of CD4(+) CD25(+) and CD25(-) T-Bet, GATA-3, Foxp3 and RORt cells in allergic inflammation, local lung distribution and chemokine gene expression.PLoS One. 2011;6(5):e19889. doi: 10.1371/journal.pone.0019889. Epub 2011 May 19.
5 CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration.J Neurol. 2009 Aug;256(8):1379-81. doi: 10.1007/s00415-009-5138-y. Epub 2009 May 5.
6 Common and differential chemokine expression patterns in rs cells of NLP, EBV positive and negative classical Hodgkin lymphomas.Int J Cancer. 2002 Jun 10;99(5):665-72. doi: 10.1002/ijc.10399.
7 Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: a comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol.J Crohns Colitis. 2013 Sep;7(8):622-30. doi: 10.1016/j.crohns.2012.08.015. Epub 2012 Sep 24.
8 CCL8 and the Immune Control of Cytomegalovirus in Organ Transplant Recipients.Am J Transplant. 2015 Jul;15(7):1882-92. doi: 10.1111/ajt.13207. Epub 2015 Mar 12.
9 The peroxisome proliferator-activated receptor-/ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.Exp Eye Res. 2020 Jan;190:107885. doi: 10.1016/j.exer.2019.107885. Epub 2019 Nov 20.
10 Chemokine Network and Overall Survival in TP53 Wild-Type and Mutant Ovarian Cancer.Immune Netw. 2018 Aug 13;18(4):e29. doi: 10.4110/in.2018.18.e29. eCollection 2018 Aug.
11 MCP2 activates NF-B signaling pathway promoting the migration and invasion of ESCC cells.Cell Biol Int. 2018 Mar;42(3):365-372. doi: 10.1002/cbin.10909. Epub 2017 Nov 22.
12 Upregulation of plasma CCL8 in mouse model of graft-vs-host disease.Exp Hematol. 2009 Apr;37(4):525-31. doi: 10.1016/j.exphem.2008.12.006.
13 Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients.Mem Inst Oswaldo Cruz. 2011 Dec;106(8):1007-13. doi: 10.1590/s0074-02762011000800018.
14 Primary osteoarthritis in the ankle joint is associated with finger metacarpophalangeal osteoarthritis and the H63D mutation in the HFE gene: evidence for a hemochromatosis-like polyarticular osteoarthritis phenotype.J Clin Rheumatol. 2006 Jun;12(3):109-13. doi: 10.1097/01.rhu.0000221800.77223.d6.
15 A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
16 MiR-345-5p functions as a tumor suppressor in pancreatic cancer by directly targeting CCL8.Biomed Pharmacother. 2019 Mar;111:891-900. doi: 10.1016/j.biopha.2018.12.121. Epub 2019 Jan 7.
17 Polymorphisms of key chemokine genes and survival of non-small cell lung cancer in Chinese.Lung Cancer. 2011 Nov;74(2):164-9. doi: 10.1016/j.lungcan.2011.03.005. Epub 2011 Apr 22.
18 Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue: characterization of interstitial concentration and regulation of gene expression by insulin.J Clin Endocrinol Metab. 2007 Jul;92(7):2688-95. doi: 10.1210/jc.2006-2814. Epub 2007 Apr 24.
19 Next stop: Perivasculature! ILC2s hitch a ride on the CCL8 express.Sci Immunol. 2019 Jun 7;4(36):eaax4583. doi: 10.1126/sciimmunol.aax4583. Epub 2019 Jun 7.
20 The CC chemokines CCL8, CCL13 and CCL20 are local inflammatory biomarkers of HLA-B27-associated uveitis.Acta Ophthalmol. 2019 Feb;97(1):e122-e128. doi: 10.1111/aos.13835. Epub 2018 Sep 21.
21 Is joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis explained by subclinical inflammation? A cross-sectional MRI study.Rheumatology (Oxford). 2019 Jan 1;58(1):86-93. doi: 10.1093/rheumatology/key220.
22 Moxibustion treatment modulates the gut microbiota and immune function in a dextran sulphate sodium-induced colitis rat model.World J Gastroenterol. 2018 Jul 28;24(28):3130-3144. doi: 10.3748/wjg.v24.i28.3130.
23 Weighted gene correlation network analysis identifies RSAD2, HERC5, and CCL8 as prognostic candidates for breast cancer.J Cell Physiol. 2020 Jan;235(1):394-407. doi: 10.1002/jcp.28980. Epub 2019 Jun 21.
24 The importance of microenvironment: the role of CCL8 in metastasis formation of melanoma.Oncotarget. 2015 Oct 6;6(30):29111-28. doi: 10.18632/oncotarget.5059.
25 Bortezomib restores stroma-mediated APO2L/TRAIL apoptosis resistance in multiple myeloma. Eur J Haematol. 2010 Mar;84(3):212-22. doi: 10.1111/j.1600-0609.2009.01381.x. Epub 2009 Nov 17.
26 What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?.Arthritis Res Ther. 2019 Feb 14;21(1):56. doi: 10.1186/s13075-019-1845-7.
27 Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.Physiol Genomics. 2018 May 1;50(5):299-312. doi: 10.1152/physiolgenomics.00122.2017. Epub 2018 Mar 9.
28 Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2.Sci Signal. 2017 May 23;10(480):eaai8529. doi: 10.1126/scisignal.aai8529.
29 HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 microg/L are at low risk of hemochromatosis.Hepatology. 2010 Sep;52(3):925-33. doi: 10.1002/hep.23786.
30 Mechanisms of IFN--induced apoptosis of human skin keratinocytes in patients with atopic dermatitis.J Allergy Clin Immunol. 2012 May;129(5):1297-306. doi: 10.1016/j.jaci.2012.02.020. Epub 2012 Mar 24.
31 Differences in the degree of cerulein-induced chronic pancreatitis in C57BL/6 mouse substrains lead to new insights in identification of potential risk factors in the development of chronic pancreatitis.Am J Pathol. 2013 Sep;183(3):692-708. doi: 10.1016/j.ajpath.2013.05.020. Epub 2013 Jul 8.
32 MicroRNA-146a-5p attenuates visceral hypersensitivity through targeting chemokine CCL8 in the spinal cord in a mouse model of colitis.Brain Res Bull. 2018 May;139:235-242. doi: 10.1016/j.brainresbull.2018.03.007. Epub 2018 Mar 14.
33 CCL8 enhances sensitivity of cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 macrophages.Photodiagnosis Photodyn Ther. 2019 Jun;26:235-243. doi: 10.1016/j.pdpdt.2019.03.014. Epub 2019 Mar 19.
34 CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis.J Neuroinflammation. 2017 Jul 10;14(1):134. doi: 10.1186/s12974-017-0907-5.
35 Semiquantitative analysis of intrahepatic CC-chemokine mRNas in chronic hepatitis C.Mediators Inflamm. 2004 Dec;13(5-6):357-9. doi: 10.1080/09629350400003159.
36 Gene expression in HIV-1/Mycobacterium tuberculosis co-infected macrophages is dominated by M. tuberculosis.Tuberculosis (Edinb). 2009 Jul;89(4):285-93. doi: 10.1016/j.tube.2009.05.003. Epub 2009 Jun 10.
37 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.
38 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
39 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
40 Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
41 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
42 Bortezomib restores stroma-mediated APO2L/TRAIL apoptosis resistance in multiple myeloma. Eur J Haematol. 2010 Mar;84(3):212-22. doi: 10.1111/j.1600-0609.2009.01381.x. Epub 2009 Nov 17.
43 Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
44 Morphine treatment of human monocyte-derived macrophages induces differential miRNA and protein expression: impact on inflammation and oxidative stress in the central nervous system. J Cell Biochem. 2010 Jul 1;110(4):834-45. doi: 10.1002/jcb.22592.
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