Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDIS99H)

DOT Name C-C motif chemokine 7 (CCL7)
Synonyms Monocyte chemoattractant protein 3; Monocyte chemotactic protein 3; MCP-3; NC28; Small-inducible cytokine A7
Gene Name CCL7
Related Disease
Crohn disease ( )
Glomerulonephritis ( )
Allergic rhinitis ( )
Allergy ( )
Atopic dermatitis ( )
Autism spectrum disorder ( )
Breast carcinoma ( )
Bronchiolitis obliterans syndrome ( )
Cardiovascular disease ( )
Cholestasis ( )
Clear cell renal carcinoma ( )
Colitis ( )
Inflammatory bowel disease ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant mesothelioma ( )
Matthew-Wood syndrome ( )
Nasal polyp ( )
Neoplasm ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoarthritis ( )
Pancreatic cancer ( )
Pneumonia ( )
Pneumonitis ( )
Promyelocytic leukaemia ( )
Psoriasis ( )
Renal cell carcinoma ( )
Cervical carcinoma ( )
Immune system disorder ( )
Interstitial nephritis ( )
Plasma cell myeloma ( )
Rheumatoid arthritis ( )
Squamous cell carcinoma ( )
Stroke ( )
Advanced cancer ( )
Arteriosclerosis ( )
Arthritis ( )
Asthma ( )
Atherosclerosis ( )
Breast cancer ( )
Colorectal carcinoma ( )
High blood pressure ( )
Methicillin-resistant staphylococci infection ( )
Non-insulin dependent diabetes ( )
Systemic sclerosis ( )
UniProt ID
CCL7_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1BO0; 1NCV; 4ZKC; 7S58; 7S59; 7SCU; 8FJ3; 8FK6; 8FK8
Pfam ID
PF00048
Sequence
MKASAALLCLLLTAAAFSPQGLAQPVGINTSTTCCYRFINKKIPKQRLESYRRTTSSHCP
REAVIFKTKLDKEICADPTQKWVQDFMKHLDKKTQTPKL
Function
Chemotactic factor that attracts monocytes and eosinophils, but not neutrophils. Augments monocyte anti-tumor activity. Also induces the release of gelatinase B. This protein can bind heparin. Binds to CCR1, CCR2 and CCR3.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
Chemokine sig.ling pathway (hsa04062 )
IL-17 sig.ling pathway (hsa04657 )
Reactome Pathway
Chemokine receptors bind chemokines (R-HSA-380108 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Crohn disease DIS2C5Q8 Definitive Genetic Variation [1]
Glomerulonephritis DISPZIQ3 Definitive Biomarker [2]
Allergic rhinitis DIS3U9HN Strong Biomarker [3]
Allergy DIS48ZAP Strong Biomarker [4]
Atopic dermatitis DISTCP41 Strong Biomarker [5]
Autism spectrum disorder DISXK8NV Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Bronchiolitis obliterans syndrome DISCK9IV Strong Biomarker [8]
Cardiovascular disease DIS2IQDX Strong Biomarker [9]
Cholestasis DISDJJWE Strong Biomarker [10]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [11]
Colitis DISAF7DD Strong Biomarker [12]
Inflammatory bowel disease DISGN23E Strong Biomarker [13]
Lung cancer DISCM4YA Strong Altered Expression [14]
Lung carcinoma DISTR26C Strong Altered Expression [14]
Malignant mesothelioma DISTHJGH Strong Biomarker [15]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [16]
Nasal polyp DISLP3XE Strong Altered Expression [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Neuroblastoma DISVZBI4 Strong Biomarker [19]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [20]
Obesity DIS47Y1K Strong Biomarker [21]
Osteoarthritis DIS05URM Strong Biomarker [22]
Pancreatic cancer DISJC981 Strong Biomarker [16]
Pneumonia DIS8EF3M Strong Biomarker [4]
Pneumonitis DIS88E0K Strong Biomarker [4]
Promyelocytic leukaemia DISYGG13 Strong Biomarker [23]
Psoriasis DIS59VMN Strong Biomarker [24]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [11]
Cervical carcinoma DIST4S00 moderate Biomarker [25]
Immune system disorder DISAEGPH moderate Altered Expression [26]
Interstitial nephritis DISKQGND moderate Biomarker [27]
Plasma cell myeloma DIS0DFZ0 moderate Genetic Variation [28]
Rheumatoid arthritis DISTSB4J moderate Biomarker [29]
Squamous cell carcinoma DISQVIFL moderate Biomarker [30]
Stroke DISX6UHX moderate Altered Expression [31]
Advanced cancer DISAT1Z9 Limited Biomarker [14]
Arteriosclerosis DISK5QGC Limited Biomarker [32]
Arthritis DIST1YEL Limited Altered Expression [33]
Asthma DISW9QNS Limited Altered Expression [34]
Atherosclerosis DISMN9J3 Limited Biomarker [32]
Breast cancer DIS7DPX1 Limited Altered Expression [35]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [36]
High blood pressure DISY2OHH Limited Biomarker [37]
Methicillin-resistant staphylococci infection DIS6DRDZ Limited Biomarker [38]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [32]
Systemic sclerosis DISF44L6 Limited Biomarker [39]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of C-C motif chemokine 7 (CCL7). [40]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of C-C motif chemokine 7 (CCL7). [23]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of C-C motif chemokine 7 (CCL7). [42]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of C-C motif chemokine 7 (CCL7). [23]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of C-C motif chemokine 7 (CCL7). [43]
Malathion DMXZ84M Approved Malathion increases the expression of C-C motif chemokine 7 (CCL7). [44]
Isoproterenol DMK7MEY Approved Isoproterenol decreases the expression of C-C motif chemokine 7 (CCL7). [45]
Abexinostat DM91LGU Phase 3 Abexinostat decreases the expression of C-C motif chemokine 7 (CCL7). [46]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the expression of C-C motif chemokine 7 (CCL7). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of C-C motif chemokine 7 (CCL7). [48]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of C-C motif chemokine 7 (CCL7). [49]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of C-C motif chemokine 7 (CCL7). [51]
Manganese DMKT129 Investigative Manganese increases the expression of C-C motif chemokine 7 (CCL7). [52]
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⏷ Show the Full List of 12 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Nickel chloride DMI12Y8 Investigative Nickel chloride decreases the secretion of C-C motif chemokine 7 (CCL7). [50]
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References

1 Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease.Hum Mol Genet. 2010 Sep 1;19(17):3468-76. doi: 10.1093/hmg/ddq248. Epub 2010 Jun 22.
2 Effective methylprednisolone dose in experimental crescentic glomerulonephritis.Am J Kidney Dis. 2001 Feb;37(2):411-7. doi: 10.1053/ajkd.2001.21329.
3 Role of Interleukin-17A on the Chemotactic Responses to CCL7 in a Murine Allergic Rhinitis Model.PLoS One. 2017 Jan 3;12(1):e0169353. doi: 10.1371/journal.pone.0169353. eCollection 2017.
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 Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis.Ann Allergy Asthma Immunol. 2020 Jan;124(1):70-78. doi: 10.1016/j.anai.2019.10.013. Epub 2019 Oct 14.
6 Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes.J Neuroimmunol. 2011 Sep 15;238(1-2):73-80. doi: 10.1016/j.jneuroim.2011.07.001. Epub 2011 Jul 30.
7 Regulation of MCP-3 and BRCA2 mRNA expression levels by beta(1) integrins.Exp Mol Pathol. 2001 Jun;70(3):239-47. doi: 10.1006/exmp.2001.2359.
8 Bronchial and bronchiolar fibrosis in rats exposed to 2,3-pentanedione vapors: implications for bronchiolitis obliterans in humans.Toxicol Pathol. 2012 Apr;40(3):448-65. doi: 10.1177/0192623311431946. Epub 2012 Jan 3.
9 CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Leishmania major Infection.Front Immunol. 2019 Jan 8;9:3063. doi: 10.3389/fimmu.2018.03063. eCollection 2018.
10 Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis.Am J Pathol. 2011 Jan;178(1):175-86. doi: 10.1016/j.ajpath.2010.11.026. Epub 2010 Dec 23.
11 Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7.Mol Cancer. 2014 Sep 6;13:206. doi: 10.1186/1476-4598-13-206.
12 Dipotassium Glycyrrhizate Improves Intestinal Mucosal Healing by Modulating Extracellular Matrix Remodeling Genes and Restoring Epithelial Barrier Functions.Front Immunol. 2019 Apr 26;10:939. doi: 10.3389/fimmu.2019.00939. eCollection 2019.
13 Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa.Gut. 1999 May;44(5):629-35. doi: 10.1136/gut.44.5.629.
14 High CCL7 expression is associated with migration, invasion and bone metastasis of non-small cell lung cancer cells.Am J Transl Res. 2019 Jan 15;11(1):442-452. eCollection 2019.
15 Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area.PLoS One. 2014 Aug 27;9(8):e104848. doi: 10.1371/journal.pone.0104848. eCollection 2014.
16 Antitumoral activity of parvovirus-mediated IL-2 and MCP-3/CCL7 delivery into human pancreatic cancer: implication of leucocyte recruitment.Cancer Immunol Immunother. 2012 Nov;61(11):2113-23. doi: 10.1007/s00262-012-1279-4. Epub 2012 May 11.
17 Increased eotaxin-mRNA expression in non-atopic and atopic nasal polyps: comparison to RANTES and MCP-3 expression.Rhinology. 1997 Dec;35(4):171-4.
18 Isocytosine deaminase Vcz as a novel tool for the prodrug cancer therapy.BMC Cancer. 2019 Mar 4;19(1):197. doi: 10.1186/s12885-019-5409-7.
19 Constitutional translocation t(1;17)(p36.31-p36.13;q11.2-q12.1) in a neuroblastoma patient. Establishment of somatic cell hybrids and identification of PND/A12M2 on chromosome 1 and NF1/SCYA7 on chromosome 17 as breakpoint flanking single copy markers.Oncogene. 1995 Mar 16;10(6):1087-93.
20 The expression and correlation between chemokine CCL7 and ABCE1 in non-small cell lung cancer.Exp Ther Med. 2018 Oct;16(4):3004-3010. doi: 10.3892/etm.2018.6568. Epub 2018 Aug 2.
21 Expression of monocyte chemotactic protein 3 following simulated birth trauma in a murine model of obesity.Urology. 2010 Dec;76(6):1517.e12-7. doi: 10.1016/j.urology.2010.07.466. Epub 2010 Oct 23.
22 An initial investigation into endothelial CC chemokine expression in the human rheumatoid synovium.Cytokine. 2017 Sep;97:133-140. doi: 10.1016/j.cyto.2017.05.023.
23 Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009 Dec 24;114(27):5512-21. doi: 10.1182/blood-2009-02-204834. Epub 2009 Oct 14.
24 CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin.Exp Dermatol. 2015 Jul;24(7):522-8. doi: 10.1111/exd.12709. Epub 2015 May 4.
25 Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts.J Gene Med. 2001 Jul-Aug;3(4):326-37. doi: 10.1002/jgm.191.
26 Crucial biological functions of CCL7 in cancer.PeerJ. 2018 Jun 14;6:e4928. doi: 10.7717/peerj.4928. eCollection 2018.
27 Gene expression of CC chemokines in experimental acute tubulointerstitial nephritis.J Lab Clin Med. 1999 Jan;133(1):41-7. doi: 10.1053/lc.1999.v133.a94726.
28 Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated pre-diagnostic blood samples.Haematologica. 2019 Dec;104(12):2456-2464. doi: 10.3324/haematol.2019.216895. Epub 2019 Apr 4.
29 Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis.Arthritis Res Ther. 2019 Jul 12;21(1):172. doi: 10.1186/s13075-019-1939-2.
30 Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7.Int J Cancer. 2010 Jul 15;127(2):332-44. doi: 10.1002/ijc.25060.
31 Molecular cloning and expression of the rat monocyte chemotactic protein-3 gene: a possible role in stroke.Brain Res Mol Brain Res. 1999 Aug 25;71(2):304-12. doi: 10.1016/s0169-328x(99)00203-x.
32 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.
33 Antigen-induced differential gene expression in lymphocytes and gene expression profile in synovium prior to the onset of arthritis.Autoimmunity. 2006 Dec;39(8):663-73. doi: 10.1080/08916930601062643.
34 Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP-3 in symptomatic atopic and nonatopic asthmatics: relationship to the eosinophil-active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor, and IL-3.Am J Respir Cell Mol Biol. 1997 Jan;16(1):1-8. doi: 10.1165/ajrcmb.16.1.8998072.
35 Induction of the MCP chemokine cluster cascade in the periphery by cancer cell-derived Ccl3.Cancer Lett. 2017 Mar 28;389:49-58. doi: 10.1016/j.canlet.2016.12.028. Epub 2016 Dec 29.
36 Effect of Chemokine (C-C Motif) Ligand 7 (CCL7) and Its Receptor (CCR2) Expression on Colorectal Cancer Behaviors.Int J Mol Sci. 2019 Feb 5;20(3):686. doi: 10.3390/ijms20030686.
37 Hypoxia inducible factor 1 in vascular smooth muscle cells promotes angiotensin II-induced vascular remodeling via activation of CCL7-mediated macrophage recruitment.Cell Death Dis. 2019 Jul 18;10(8):544. doi: 10.1038/s41419-019-1757-0.
38 Sensitizing of -lactam resistance by tannic acid in methicillin-resistant S. aureus.World J Microbiol Biotechnol. 2019 Mar 21;35(4):57. doi: 10.1007/s11274-019-2637-6.
39 Up regulated expression of tumour necrosis factor {alpha} converting enzyme in peripheral monocytes of patients with early systemic sclerosis.Ann Rheum Dis. 2005 Aug;64(8):1165-73. doi: 10.1136/ard.2004.030338.
40 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.
41 Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009 Dec 24;114(27):5512-21. doi: 10.1182/blood-2009-02-204834. Epub 2009 Oct 14.
42 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.
43 Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
44 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
45 Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):302-12.
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47 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
48 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
49 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
50 Ni(II) ions dysregulate cytokine secretion from human monocytes. J Biomed Mater Res B Appl Biomater. 2009 Feb;88(2):358-65. doi: 10.1002/jbm.b.31063.
51 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
52 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.