Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6XNQ7)

DOT Name C-C motif chemokine 28 (CCL28)
Synonyms Mucosae-associated epithelial chemokine; MEC; Protein CCK1; Small-inducible cytokine A28
Gene Name CCL28
Related Disease
Cone-rod dystrophy 2 ( )
Nephropathy ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cholelithiasis ( )
Chronic obstructive pulmonary disease ( )
Colitis ( )
Duchenne muscular dystrophy ( )
Esophageal squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
HIV infectious disease ( )
Influenza ( )
Liver cancer ( )
Liver cirrhosis ( )
Lung carcinoma ( )
Metabolic disorder ( )
Metastatic malignant neoplasm ( )
Myelodysplastic syndrome ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Pancreatic tumour ( )
Rheumatoid arthritis ( )
Skin disease ( )
Small lymphocytic lymphoma ( )
Systemic lupus erythematosus ( )
T-cell leukaemia ( )
Tarsal-carpal coalition syndrome ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
Transitional cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Acute myelogenous leukaemia ( )
Lung adenocarcinoma ( )
Osteoarthritis ( )
Arthritis ( )
Advanced cancer ( )
Asthma ( )
Dental caries ( )
Gallbladder carcinoma ( )
Lung neoplasm ( )
Pancreatic cancer ( )
UniProt ID
CCL28_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6CWS
Pfam ID
PF00048
Sequence
MQQRGLAIVALAVCAALHASEAILPIASSCCTEVSHHISRRLLERVNMCRIQRADGDCDL
AAVILHVKRRRICVSPHNHTVKQWMKVQAAKKNGKGNVCHRKKHHGKRNSNRAHQGKHET
YGHKTPY
Function Chemotactic activity for resting CD4, CD8 T-cells and eosinophils. Binds to CCR3 and CCR10 and induces calcium mobilization in a dose-dependent manner.
Tissue Specificity
Preferentially expressed by epithelial cells of diverse tissues including normal and pathological colon, salivary gland, mammary gland, trachea and rectum. Also found in prostate, spleen, thyroid, psoriasis skin and in lower levels in peripheral blood leukocytes, small intestine, Peyer patches, stomach and normal skin.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
Chemokine sig.ling pathway (hsa04062 )
Intesti.l immune network for IgA production (hsa04672 )
Reactome Pathway
G alpha (i) signalling events (R-HSA-418594 )
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
Cone-rod dystrophy 2 DISX2RWY Definitive Biomarker [1]
Nephropathy DISXWP4P Definitive Genetic Variation [2]
Bladder cancer DISUHNM0 Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Biomarker [4]
Breast carcinoma DIS2UE88 Strong Biomarker [4]
Breast neoplasm DISNGJLM Strong Altered Expression [5]
Carcinoma DISH9F1N Strong Altered Expression [6]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Biomarker [7]
Cholelithiasis DISERLZB Strong Biomarker [8]
Chronic obstructive pulmonary disease DISQCIRF Strong Genetic Variation [9]
Colitis DISAF7DD Strong Biomarker [10]
Duchenne muscular dystrophy DISRQ3NV Strong Biomarker [11]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [12]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [7]
High blood pressure DISY2OHH Strong Biomarker [13]
HIV infectious disease DISO97HC Strong Genetic Variation [14]
Influenza DIS3PNU3 Strong Biomarker [15]
Liver cancer DISDE4BI Strong Biomarker [7]
Liver cirrhosis DIS4G1GX Strong Biomarker [16]
Lung carcinoma DISTR26C Strong Posttranslational Modification [17]
Metabolic disorder DIS71G5H Strong Biomarker [18]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [19]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [22]
Obesity DIS47Y1K Strong Genetic Variation [22]
Pancreatic tumour DIS3U0LK Strong Altered Expression [6]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [23]
Skin disease DISDW8R6 Strong Biomarker [24]
Small lymphocytic lymphoma DIS30POX Strong Genetic Variation [25]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [26]
T-cell leukaemia DISJ6YIF Strong Biomarker [27]
Tarsal-carpal coalition syndrome DISY90L2 Strong Biomarker [3]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W Strong Biomarker [28]
Transitional cell carcinoma DISWVVDR Strong Biomarker [3]
Urinary bladder cancer DISDV4T7 Strong Biomarker [3]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [3]
Acute myelogenous leukaemia DISCSPTN moderate Biomarker [29]
Lung adenocarcinoma DISD51WR moderate Altered Expression [30]
Osteoarthritis DIS05URM moderate Altered Expression [23]
Arthritis DIST1YEL Disputed Altered Expression [31]
Advanced cancer DISAT1Z9 Limited Biomarker [32]
Asthma DISW9QNS Limited Biomarker [33]
Dental caries DISRBCMD Limited Biomarker [34]
Gallbladder carcinoma DISD6ACL Limited Biomarker [35]
Lung neoplasm DISVARNB Limited Biomarker [36]
Pancreatic cancer DISJC981 Limited Biomarker [37]
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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
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the expression of C-C motif chemokine 28 (CCL28). [38]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of C-C motif chemokine 28 (CCL28). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of C-C motif chemokine 28 (CCL28). [40]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of C-C motif chemokine 28 (CCL28). [41]
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References

1 CCL28 promotes locomotor recovery after spinal cord injury via recruiting regulatory T cells.Aging (Albany NY). 2019 Sep 26;11(18):7402-7415. doi: 10.18632/aging.102239. Epub 2019 Sep 26.
2 A disease-causing mutation illuminates the protein membrane topology of the kidney-expressed prohibitin homology (PHB) domain protein podocin.J Biol Chem. 2014 Apr 18;289(16):11262-11271. doi: 10.1074/jbc.M113.521773. Epub 2014 Mar 4.
3 Establishment and characterization of two human bladder cancer cell lines.Hum Cell. 1996 Mar;9(1):49-56.
4 Complicated prognostic values of CCL28 in breast cancer by subtype.J Thorac Dis. 2019 Mar;11(3):777-787. doi: 10.21037/jtd.2019.02.26.
5 Identification of a novel beta-chemokine, MEC, down-regulated in primary breast tumors.Int J Oncol. 2001 May;18(5):939-44. doi: 10.3892/ijo.18.5.939.
6 Distribution of CCK1 and CCK2 receptors in normal and diseased human pancreatic tissue.Gastroenterology. 2003 Jul;125(1):98-106. doi: 10.1016/s0016-5085(03)00697-8.
7 Hypoxia-induced CCL28 promotes recruitment of regulatory T cells and tumor growth in liver cancer.Oncotarget. 2016 Nov 15;7(46):75763-75773. doi: 10.18632/oncotarget.12409.
8 Update on the Molecular Mechanisms Underlying the Effect of Cholecystokinin and Cholecystokinin-1 Receptor on the Formation of Cholesterol Gallstones.Curr Med Chem. 2019;26(19):3407-3423. doi: 10.2174/0929867324666170619104801.
9 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
10 CCL28-Deficient Mice Have Reduced IgA Antibody-Secreting Cells and an Altered Microbiota in the Colon.J Immunol. 2018 Jan 15;200(2):800-809. doi: 10.4049/jimmunol.1700037. Epub 2017 Dec 13.
11 Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin.Cell Mol Life Sci. 2017 Jul;74(13):2487-2501. doi: 10.1007/s00018-017-2465-5. Epub 2017 Feb 10.
12 A truncated splice variant of human lysyl oxidase-like 2 promotes migration and invasion in esophageal squamous cell carcinoma.Int J Biochem Cell Biol. 2016 Jun;75:85-98. doi: 10.1016/j.biocel.2016.04.003. Epub 2016 Apr 8.
13 Serum cytokine profiles in patients with chronic obstructive pulmonary disease associated pulmonary hypertension identified using protein array.Cytokine. 2018 Nov;111:342-349. doi: 10.1016/j.cyto.2018.09.005. Epub 2018 Sep 28.
14 Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection.MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):990-994. doi: 10.15585/mmwr.mm6637a6.
15 Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses.Sci Rep. 2017 Jan 9;7:40226. doi: 10.1038/srep40226.
16 Whole genome expression profiling and screening for differentially expressed cytokine genes in human bone marrow endothelial cells treated with humoral inhibitors in liver cirrhosis.Int J Mol Med. 2013 Nov;32(5):1204-14. doi: 10.3892/ijmm.2013.1495. Epub 2013 Sep 13.
17 Primary Pulmonary Mucoepidermoid Carcinoma: Histopathological and Moleculargenetic Studies of 26 Cases.PLoS One. 2015 Nov 17;10(11):e0143169. doi: 10.1371/journal.pone.0143169. eCollection 2015.
18 Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases.Curr Top Med Chem. 2007;7(12):1211-31. doi: 10.2174/156802607780960519.
19 Quantitative expression profiling of G-protein-coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target.Pigment Cell Melanoma Res. 2011 Feb;24(1):207-18. doi: 10.1111/j.1755-148X.2010.00781.x. Epub 2010 Oct 21.
20 Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995).J Clin Oncol. 2004 Mar 15;22(6):1078-86. doi: 10.1200/JCO.2004.07.048.
21 CCL28-induced RAR expression inhibits oral squamous cell carcinoma bone invasion.J Clin Invest. 2019 Dec 2;129(12):5381-5399. doi: 10.1172/JCI125336.
22 Exercise initiated after the onset of insulin resistance improves trabecular microarchitecture and cortical bone biomechanics of the tibia in hyperphagic Otsuka Long Evans Tokushima Fatty rats.Bone. 2017 Oct;103:188-199. doi: 10.1016/j.bone.2017.07.010. Epub 2017 Jul 12.
23 Th22 Cells Promote Osteoclast Differentiation via Production of IL-22 in Rheumatoid Arthritis.Front Immunol. 2018 Dec 10;9:2901. doi: 10.3389/fimmu.2018.02901. eCollection 2018.
24 CCL28 production in HaCaT cells was mediated by different signal pathways from CCL27.Exp Dermatol. 2006 Feb;15(2):95-100. doi: 10.1111/j.1600-0625.2005.00390.x.
25 Targeting B-cell malignancies with the beta-emitting anti-CD37 radioimmunoconjugate (177)Lu-NNV003.Eur J Nucl Med Mol Imaging. 2019 Oct;46(11):2311-2321. doi: 10.1007/s00259-019-04417-1. Epub 2019 Jul 15.
26 Plasmablasts With a Mucosal Phenotype Contribute to Plasmacytosis in Systemic Lupus Erythematosus.Arthritis Rheumatol. 2017 Oct;69(10):2018-2028. doi: 10.1002/art.40181.
27 Modifying akt signaling in B-cell chronic lymphocytic leukemia cells.Cancer Res. 2010 Sep 15;70(18):7336-44. doi: 10.1158/0008-5472.CAN-09-4411. Epub 2010 Sep 7.
28 Bioinformatics analysis of key genes and latent pathway interactions based on the anaplastic thyroid carcinoma gene expression profile.Oncol Lett. 2017 Jan;13(1):167-176. doi: 10.3892/ol.2016.5447. Epub 2016 Nov 30.
29 A Phase I/II Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed Refractory Acute Myeloid Leukemia.Clin Cancer Res. 2019 Jul 15;25(14):4231-4237. doi: 10.1158/1078-0432.CCR-18-3886. Epub 2019 Apr 16.
30 Hypoxia induced CCL28 promotes angiogenesis in lung adenocarcinoma by targeting CCR3 on endothelial cells.Sci Rep. 2016 Jun 2;6:27152. doi: 10.1038/srep27152.
31 Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis.Ann Rheum Dis. 2015 Oct;74(10):1898-906. doi: 10.1136/annrheumdis-2013-204530. Epub 2014 May 15.
32 Cost-utility analysis of aprepitant for patients who truly need it in Japan.Support Care Cancer. 2019 Oct;27(10):3749-3758. doi: 10.1007/s00520-019-04672-w. Epub 2019 Feb 1.
33 IL-1beta and TNF-alpha induce increased expression of CCL28 by airway epithelial cells via an NFkappaB-dependent pathway.Cell Immunol. 2005 Dec;238(2):87-96. doi: 10.1016/j.cellimm.2006.02.003. Epub 2006 Apr 11.
34 Enhancing CCL28 expression through the gene transfer to salivary glands for controlling cariogenic microbe.Cytokine. 2012 Jul;59(1):94-9. doi: 10.1016/j.cyto.2012.03.022. Epub 2012 Apr 13.
35 CCK1 receptor is involved in the regulation of protein lysine acetylation in GBC-SD cells and gallbladder carcinoma.Ir J Med Sci. 2017 Nov;186(4):883-888. doi: 10.1007/s11845-017-1603-2. Epub 2017 May 3.
36 Influence of Neutron Sources and 10B Concentration on Boron Neutron Capture Therapy for Shallow and Deeper Non-small Cell Lung Cancer.Health Phys. 2017 Mar;112(3):258-265. doi: 10.1097/HP.0000000000000601.
37 Cancer cell chemokines direct chemotaxis of activated stellate cells in pancreatic ductal adenocarcinoma.Lab Invest. 2017 Mar;97(3):302-317. doi: 10.1038/labinvest.2016.146. Epub 2017 Jan 16.
38 Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
39 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
40 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
41 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.