Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFTCQ4O)

DOT Name C-X-C motif chemokine 6 (CXCL6)
Synonyms Chemokine alpha 3; CKA-3; Granulocyte chemotactic protein 2; GCP-2; Small-inducible cytokine B6
Gene Name CXCL6
Related Disease
Alcoholic liver diseases ( )
Adult glioblastoma ( )
Astrocytoma ( )
Behcet disease ( )
Bone osteosarcoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Craniosynostosis ( )
Cutaneous mastocytosis ( )
Cystic fibrosis ( )
Diabetic kidney disease ( )
Hepatocellular carcinoma ( )
Isolated congenital microcephaly ( )
Juvenile idiopathic arthritis ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Myocardial infarction ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Osteosarcoma ( )
Systemic sclerosis ( )
Ulcerative colitis ( )
Vascular disease ( )
Advanced cancer ( )
Age-related macular degeneration ( )
Glycogen storage disease type II ( )
Neoplasm ( )
Neural tube defect ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Arthritis ( )
Chronic hepatitis B virus infection ( )
Colorectal carcinoma ( )
Coronary heart disease ( )
Crohn disease ( )
Glaucoma/ocular hypertension ( )
Glioblastoma multiforme ( )
Rheumatoid arthritis ( )
Severe acute respiratory syndrome (SARS) ( )
UniProt ID
CXCL6_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00048
Sequence
MSLPSSRAARVPGPSGSLCALLALLLLLTPPGPLASAGPVSAVLTELRCTCLRVTLRVNP
KTIGKLQVFPAGPQCSKVEVVASLKNGKQVCLDPEAPFLKKVIQKILDSGNKKN
Function
Chemotactic for neutrophil granulocytes. Signals through binding and activation of its receptors (CXCR1 and CXCR2). In addition to its chemotactic and angiogenic properties, it has strong antibacterial activity against Gram-positive and Gram-negative bacteria (90-fold-higher when compared to CXCL5 and CXCL7).
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 )
TNF sig.ling pathway (hsa04668 )
Pertussis (hsa05133 )
Rheumatoid arthritis (hsa05323 )
Reactome Pathway
G alpha (i) signalling events (R-HSA-418594 )
Chemokine receptors bind chemokines (R-HSA-380108 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alcoholic liver diseases DISXEPHQ Definitive Biomarker [1]
Adult glioblastoma DISVP4LU Strong Altered Expression [2]
Astrocytoma DISL3V18 Strong Altered Expression [2]
Behcet disease DISSYMBS Strong Altered Expression [3]
Bone osteosarcoma DIST1004 Strong Biomarker [4]
Cervical cancer DISFSHPF Strong Biomarker [5]
Cervical carcinoma DIST4S00 Strong Biomarker [5]
Colon cancer DISVC52G Strong Biomarker [6]
Colon carcinoma DISJYKUO Strong Altered Expression [6]
Craniosynostosis DIS6J405 Strong Biomarker [7]
Cutaneous mastocytosis DISLBZEF Strong Biomarker [8]
Cystic fibrosis DIS2OK1Q Strong Biomarker [9]
Diabetic kidney disease DISJMWEY Strong Biomarker [10]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Isolated congenital microcephaly DISUXHZ6 Strong Genetic Variation [12]
Juvenile idiopathic arthritis DISQZGBV Strong Biomarker [13]
Lung cancer DISCM4YA Strong Biomarker [14]
Lung carcinoma DISTR26C Strong Biomarker [14]
Melanoma DIS1RRCY Strong Biomarker [15]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [15]
Myocardial infarction DIS655KI Strong Biomarker [8]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [16]
Osteoarthritis DIS05URM Strong Altered Expression [3]
Osteosarcoma DISLQ7E2 Strong Biomarker [4]
Systemic sclerosis DISF44L6 Strong Biomarker [17]
Ulcerative colitis DIS8K27O Strong Biomarker [18]
Vascular disease DISVS67S Strong Biomarker [17]
Advanced cancer DISAT1Z9 moderate Biomarker [19]
Age-related macular degeneration DIS0XS2C moderate Biomarker [20]
Glycogen storage disease type II DISXZPBC moderate Biomarker [20]
Neoplasm DISZKGEW moderate Biomarker [2]
Neural tube defect DIS5J95E Disputed Genetic Variation [21]
Prostate cancer DISF190Y Disputed Altered Expression [22]
Prostate carcinoma DISMJPLE Disputed Altered Expression [22]
Prostate neoplasm DISHDKGQ Disputed Altered Expression [22]
Arthritis DIST1YEL Limited Biomarker [23]
Chronic hepatitis B virus infection DISHL4NT Limited Altered Expression [24]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [25]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [26]
Crohn disease DIS2C5Q8 Limited Altered Expression [27]
Glaucoma/ocular hypertension DISLBXBY Limited Altered Expression [28]
Glioblastoma multiforme DISK8246 Limited Altered Expression [2]
Rheumatoid arthritis DISTSB4J Limited Biomarker [29]
Severe acute respiratory syndrome (SARS) DISYW14W Limited Biomarker [30]
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⏷ Show the Full List of 44 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 decreases the methylation of C-X-C motif chemokine 6 (CXCL6). [31]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of C-X-C motif chemokine 6 (CXCL6). [42]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of C-X-C motif chemokine 6 (CXCL6). [32]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of C-X-C motif chemokine 6 (CXCL6). [33]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of C-X-C motif chemokine 6 (CXCL6). [34]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of C-X-C motif chemokine 6 (CXCL6). [35]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of C-X-C motif chemokine 6 (CXCL6). [36]
Folic acid DMEMBJC Approved Folic acid decreases the expression of C-X-C motif chemokine 6 (CXCL6). [37]
Vitamin C DMXJ7O8 Approved Vitamin C increases the expression of C-X-C motif chemokine 6 (CXCL6). [38]
Beta-carotene DM0RXBT Approved Beta-carotene increases the expression of C-X-C motif chemokine 6 (CXCL6). [39]
Ritonavir DMU764S Approved Ritonavir decreases the expression of C-X-C motif chemokine 6 (CXCL6). [40]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of C-X-C motif chemokine 6 (CXCL6). [41]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of C-X-C motif chemokine 6 (CXCL6). [43]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of C-X-C motif chemokine 6 (CXCL6). [44]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of C-X-C motif chemokine 6 (CXCL6). [45]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of C-X-C motif chemokine 6 (CXCL6). [46]
Manganese DMKT129 Investigative Manganese increases the expression of C-X-C motif chemokine 6 (CXCL6). [47]
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⏷ Show the Full List of 15 Drug(s)

References

1 Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat.Hepatology. 1999 Oct;30(4):934-43. doi: 10.1002/hep.510300402.
2 Overexpression and Nucleolar Localization of -Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma.J Neuropathol Exp Neurol. 2015 Jul;74(7):723-42. doi: 10.1097/NEN.0000000000000212.
3 Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 designate chronicity of synovitis?.Rheumatol Int. 2007 Aug;27(10):969-73. doi: 10.1007/s00296-007-0317-6. Epub 2007 Jan 31.
4 Characterization of synthetic human granulocyte chemotactic protein 2: usage of chemokine receptors CXCR1 and CXCR2 and in vivo inflammatory properties.Biochemistry. 1997 Mar 4;36(9):2716-23. doi: 10.1021/bi961999z.
5 MicroRNA-101-5p inhibits the growth and metastasis of cervical cancer cell by inhibiting CXCL6.Eur Rev Med Pharmacol Sci. 2019 Mar;23(5):1957-1968. doi: 10.26355/eurrev_201903_17234.
6 Fibroblast-derived CXCL12/SDF-1 promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer.World J Gastroenterol. 2017 Jul 28;23(28):5167-5178. doi: 10.3748/wjg.v23.i28.5167.
7 Primary role of growth-related oncogene-alpha and granulocyte chemotactic protein-2 as neutrophil chemoattractants in chronic rhinosinusitis.Clin Exp Allergy. 2006 Jun;36(6):748-59. doi: 10.1111/j.1365-2222.2006.02501.x.
8 Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model.Cardiovasc Res. 2012 Sep 1;95(4):495-506. doi: 10.1093/cvr/cvs224. Epub 2012 Aug 10.
9 The neutrophil-recruiting chemokine GCP-2/CXCL6 is expressed in cystic fibrosis airways and retains its functional properties after binding to extracellular DNA.Mucosal Immunol. 2016 Jan;9(1):112-23. doi: 10.1038/mi.2015.43. Epub 2015 May 20.
10 CXCL6 Promotes Renal Interstitial Fibrosis in Diabetic Nephropathy by Activating JAK/STAT3 Signaling Pathway.Front Pharmacol. 2019 Mar 25;10:224. doi: 10.3389/fphar.2019.00224. eCollection 2019.
11 HIF-1 plays a role in the chemotactic migration of hepatocarcinoma cells through the modulation of CXCL6 expression.Cell Physiol Biochem. 2014;34(5):1536-46. doi: 10.1159/000366357. Epub 2014 Oct 10.
12 Bi-allelic Pathogenic Variants in TUBGCP2 Cause Microcephaly and Lissencephaly Spectrum Disorders. Am J Hum Genet. 2019 Nov 7;105(5):1005-1015. doi: 10.1016/j.ajhg.2019.09.017. Epub 2019 Oct 17.
13 Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis.Proteomics Clin Appl. 2017 May;11(5-6):1600088. doi: 10.1002/prca.201600088. Epub 2017 Jan 17.
14 CXCL6 promotes non-small cell lung cancer cell survival and metastasis via down-regulation of miR-515-5p.Biomed Pharmacother. 2018 Jan;97:1182-1188. doi: 10.1016/j.biopha.2017.11.004. Epub 2017 Nov 11.
15 Isotypic neutralizing antibodies against mouse GCP-2/CXCL6 inhibit melanoma growth and metastasis.Cancer Lett. 2011 Mar 1;302(1):54-62. doi: 10.1016/j.canlet.2010.12.013. Epub 2011 Jan 13.
16 miRNA-101-5p inhibits the growth and aggressiveness of NSCLC cells through targeting CXCL6.Onco Targets Ther. 2019 Jan 25;12:835-848. doi: 10.2147/OTT.S184235. eCollection 2019.
17 Fli1 Deficiency Induces CXCL6 Expression in Dermal Fibroblasts and Endothelial Cells, Contributing to the Development of Fibrosis and Vasculopathy in Systemic Sclerosis.J Rheumatol. 2017 Aug;44(8):1198-1205. doi: 10.3899/jrheum.161092. Epub 2017 May 15.
18 Effect of interleukin-17 on gene expression profile of fibroblasts from Crohn's disease patients.J Crohns Colitis. 2014 Oct;8(10):1208-16. doi: 10.1016/j.crohns.2014.02.009. Epub 2014 Mar 15.
19 TSPAN12 is a critical factor for cancer-fibroblast cell contact-mediated cancer invasion.Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18691-6. doi: 10.1073/pnas.1412062112. Epub 2014 Dec 15.
20 Cytokine profiles in the aqueous humor and serum of patients with dry and treated wet age-related macular degeneration.PLoS One. 2018 Aug 29;13(8):e0203337. doi: 10.1371/journal.pone.0203337. eCollection 2018.
21 Role of parental folate pathway single nucleotide polymorphisms in altering the susceptibility to neural tube defects in South India.J Perinat Med. 2010;38(1):63-9. doi: 10.1515/jpm.2009.119.
22 Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.Oncotarget. 2016 Jul 26;7(30):48011-48026. doi: 10.18632/oncotarget.10333.
23 Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8.J Biol Chem. 2007 Apr 20;282(16):11658-66. doi: 10.1074/jbc.M607705200. Epub 2006 Dec 29.
24 CXCL6 promotes human hepatocyte proliferation through the CXCR1-NFB pathway and inhibits collagen I secretion by hepatic stellate cells.Biochem Cell Biol. 2016 Jun;94(3):229-35. doi: 10.1139/bcb-2015-0136. Epub 2016 Jan 28.
25 ELR+ CXC chemokine expression in benign and malignant colorectal conditions.BMC Cancer. 2008 Jun 25;8:178. doi: 10.1186/1471-2407-8-178.
26 Genetic and environmental influences on total plasma homocysteine and coronary artery disease (CAD) risk among South Indians.Clin Chim Acta. 2009 Jul;405(1-2):127-31. doi: 10.1016/j.cca.2009.04.015. Epub 2009 Apr 24.
27 CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue.Eur J Immunol. 2004 Jul;34(7):1992-2000. doi: 10.1002/eji.200324807.
28 Expression of CXCL6 and BBS5 that may be glaucoma relevant genes is regulated by PITX2.Gene. 2016 Nov 15;593(1):76-83. doi: 10.1016/j.gene.2016.08.019. Epub 2016 Aug 9.
29 Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display.Rheumatology (Oxford). 2004 Nov;43(11):1346-52. doi: 10.1093/rheumatology/keh347. Epub 2004 Aug 3.
30 Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response.J Gen Virol. 2009 Dec;90(Pt 12):2956-2964. doi: 10.1099/vir.0.014282-0. Epub 2009 Sep 9.
31 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.
32 Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
33 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
34 Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
35 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.
36 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
37 Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way. Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700260. Epub 2017 Nov 9.
38 Pharmacologic concentrations of ascorbic acid cause diverse influence on differential expressions of angiogenic chemokine genes in different hepatocellular carcinoma cell lines. Biomed Pharmacother. 2010 May;64(5):348-51. doi: 10.1016/j.biopha.2009.06.005. Epub 2009 Oct 22.
39 Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
40 Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31-44.
41 Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37-48. doi: 10.1007/s10557-012-6427-8.
42 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.
43 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
44 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
45 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
46 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
47 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.