Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRF3D6Y)

DOT Name Claudin-2 (CLDN2)
Synonyms SP82
Gene Name CLDN2
Related Disease
Breast neoplasm ( )
Adenoma ( )
Barrett esophagus ( )
Breast carcinoma ( )
Carcinoid tumor ( )
Carcinoma ( )
Carcinoma of esophagus ( )
Chronic pancreatitis ( )
Coeliac disease ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal neoplasm ( )
Crohn disease ( )
Esophageal adenocarcinoma ( )
Familial multiple trichoepithelioma ( )
Fibrosarcoma ( )
Gastric cancer ( )
Influenza ( )
Irritable bowel syndrome ( )
Lung adenocarcinoma ( )
Neoplasm ( )
Nephritis ( )
Nephrotic syndrome ( )
Non-small-cell lung cancer ( )
Adenocarcinoma ( )
Bacterial infection ( )
Female hypogonadism ( )
Frontotemporal dementia ( )
Pancreatitis ( )
Advanced cancer ( )
Azoospermia, obstructive, with nephrolithiasis ( )
Bone osteosarcoma ( )
Breast cancer ( )
Colitis ( )
Common variable immunodeficiency ( )
Graft-versus-host disease ( )
Hereditary chronic pancreatitis ( )
Kaposi sarcoma ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Osteosarcoma ( )
Pneumonia ( )
Squamous cell carcinoma ( )
UniProt ID
CLD2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4YYX
Pfam ID
PF00822
Sequence
MASLGLQLVGYILGLLGLLGTLVAMLLPSWKTSSYVGASIVTAVGFSKGLWMECATHSTG
ITQCDIYSTLLGLPADIQAAQAMMVTSSAISSLACIISVVGMRCTVFCQESRAKDRVAVA
GGVFFILGGLLGFIPVAWNLHGILRDFYSPLVPDSMKFEIGEALYLGIISSLFSLIAGII
LCFSCSSQRNRSNYYDAYQAQPLATRSSPRPGQPPKVKSEFNSYSLTGYV
Function Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
KEGG Pathway
Cell adhesion molecules (hsa04514 )
Tight junction (hsa04530 )
Leukocyte transendothelial migration (hsa04670 )
Pathogenic Escherichia coli infection (hsa05130 )
Hepatitis C (hsa05160 )
Reactome Pathway
Tight junction interactions (R-HSA-420029 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast neoplasm DISNGJLM Definitive Biomarker [1]
Adenoma DIS78ZEV Strong Altered Expression [2]
Barrett esophagus DIS416Y7 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Biomarker [4]
Carcinoid tumor DISMNRDC Strong Biomarker [5]
Carcinoma DISH9F1N Strong Altered Expression [6]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [3]
Chronic pancreatitis DISBUOMJ Strong Genetic Variation [7]
Coeliac disease DISIY60C Strong Altered Expression [8]
Colon cancer DISVC52G Strong Altered Expression [9]
Colon carcinoma DISJYKUO Strong Altered Expression [9]
Colorectal neoplasm DISR1UCN Strong Altered Expression [10]
Crohn disease DIS2C5Q8 Strong Genetic Variation [11]
Esophageal adenocarcinoma DISODWFP Strong Altered Expression [3]
Familial multiple trichoepithelioma DISKZAUY Strong Altered Expression [3]
Fibrosarcoma DISWX7MU Strong Biomarker [12]
Gastric cancer DISXGOUK Strong Biomarker [6]
Influenza DIS3PNU3 Strong Biomarker [13]
Irritable bowel syndrome DIS27206 Strong Altered Expression [14]
Lung adenocarcinoma DISD51WR Strong Altered Expression [15]
Neoplasm DISZKGEW Strong Altered Expression [1]
Nephritis DISQZQ70 Strong Biomarker [16]
Nephrotic syndrome DISSPSC2 Strong Altered Expression [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [17]
Adenocarcinoma DIS3IHTY moderate Altered Expression [18]
Bacterial infection DIS5QJ9S moderate Biomarker [19]
Female hypogonadism DISWASB4 moderate Altered Expression [20]
Frontotemporal dementia DISKYHXL moderate Biomarker [21]
Pancreatitis DIS0IJEF moderate Genetic Variation [22]
Advanced cancer DISAT1Z9 Limited Biomarker [4]
Azoospermia, obstructive, with nephrolithiasis DISLBW49 Limited Unknown [23]
Bone osteosarcoma DIST1004 Limited Biomarker [24]
Breast cancer DIS7DPX1 Limited Biomarker [4]
Colitis DISAF7DD Limited Altered Expression [25]
Common variable immunodeficiency DISHE7JQ Limited Biomarker [8]
Graft-versus-host disease DIS0QADF Limited Altered Expression [8]
Hereditary chronic pancreatitis DISF0J1Q Limited Autosomal dominant [26]
Kaposi sarcoma DISC1H1Z Limited Altered Expression [27]
Lung cancer DISCM4YA Limited Biomarker [28]
Lung carcinoma DISTR26C Limited Biomarker [28]
Metastatic malignant neoplasm DIS86UK6 Limited Altered Expression [29]
Nasopharyngeal carcinoma DISAOTQ0 Limited Altered Expression [30]
Osteosarcoma DISLQ7E2 Limited Biomarker [24]
Pneumonia DIS8EF3M Limited Altered Expression [31]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [3]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
20 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Claudin-2 (CLDN2). [32]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Claudin-2 (CLDN2). [33]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Claudin-2 (CLDN2). [34]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Claudin-2 (CLDN2). [35]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Claudin-2 (CLDN2). [36]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Claudin-2 (CLDN2). [37]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Claudin-2 (CLDN2). [38]
Isoniazid DM5JVS3 Approved Isoniazid increases the expression of Claudin-2 (CLDN2). [32]
Tetracycline DMZA017 Approved Tetracycline decreases the expression of Claudin-2 (CLDN2). [40]
Sanguinarine DMDINFS Approved Sanguinarine decreases the expression of Claudin-2 (CLDN2). [41]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Claudin-2 (CLDN2). [42]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Claudin-2 (CLDN2). [38]
Acadesine DM1RMF5 Phase 3 Acadesine decreases the expression of Claudin-2 (CLDN2). [43]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Claudin-2 (CLDN2). [44]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Claudin-2 (CLDN2). [46]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Claudin-2 (CLDN2). [44]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Claudin-2 (CLDN2). [47]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Claudin-2 (CLDN2). [32]
Okadaic acid DM47CO1 Investigative Okadaic acid increases the expression of Claudin-2 (CLDN2). [48]
Caffeic acid phenethyl ester DMRJKIV Investigative Caffeic acid phenethyl ester decreases the expression of Claudin-2 (CLDN2). [15]
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⏷ Show the Full List of 20 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the methylation of Claudin-2 (CLDN2). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Claudin-2 (CLDN2). [45]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Claudin-2 (CLDN2). [39]
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References

1 Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in an HER2 transgenic model.Carcinogenesis. 2018 Jan 12;39(1):47-55. doi: 10.1093/carcin/bgx097.
2 Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation.Lab Invest. 2008 Oct;88(10):1110-20. doi: 10.1038/labinvest.2008.78. Epub 2008 Aug 18.
3 High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5.BMC Gastroenterol. 2017 Feb 17;17(1):33. doi: 10.1186/s12876-017-0590-0.
4 Afadin cooperates with Claudin-2 to promote breast cancer metastasis.Genes Dev. 2019 Feb 1;33(3-4):180-193. doi: 10.1101/gad.319194.118. Epub 2019 Jan 28.
5 Distinct claudin expression profile in histologic subtypes of lung cancer.Lung Cancer. 2007 Aug;57(2):159-67. doi: 10.1016/j.lungcan.2007.02.018. Epub 2007 Apr 6.
6 Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas.Virchows Arch. 2006 Apr;448(4):428-34. doi: 10.1007/s00428-005-0120-2. Epub 2005 Nov 17.
7 Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis.Pancreatology. 2018 Jul;18(5):477-481. doi: 10.1016/j.pan.2018.05.486. Epub 2018 Jun 1.
8 Differential regulation of claudin-2 and claudin-15 expression in children and adults with malabsorptive disease.Lab Invest. 2020 Mar;100(3):483-490. doi: 10.1038/s41374-019-0324-8. Epub 2019 Oct 11.
9 HDAC-4 regulates claudin-2 expression in EGFR-ERK1/2 dependent manner to regulate colonic epithelial cell differentiation.Oncotarget. 2017 Sep 23;8(50):87718-87736. doi: 10.18632/oncotarget.21190. eCollection 2017 Oct 20.
10 Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells.Cancer Res. 2018 Jun 1;78(11):2925-2938. doi: 10.1158/0008-5472.CAN-17-1869. Epub 2018 Mar 6.
11 Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease.World J Gastroenterol. 2013 Aug 14;19(30):4935-43. doi: 10.3748/wjg.v19.i30.4935.
12 Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2.Eur J Pharm Sci. 2018 May 30;117:161-167. doi: 10.1016/j.ejps.2018.02.016. Epub 2018 Feb 13.
13 Isolation and characterization of influenza C viruses in the Philippines and Japan.J Clin Microbiol. 2015 Mar;53(3):847-58. doi: 10.1128/JCM.02628-14. Epub 2014 Dec 31.
14 miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea.Gut. 2017 Sep;66(9):1537-1538. doi: 10.1136/gutjnl-2016-311477. Epub 2017 Jan 12.
15 Caffeic acid phenethyl ester down-regulates claudin-2 expression at the transcriptional and post-translational levels and enhances chemosensitivity to doxorubicin in lung adenocarcinoma A549 cells. J Nutr Biochem. 2018 Jun;56:205-214. doi: 10.1016/j.jnutbio.2018.02.016. Epub 2018 Mar 2.
16 Ectopic expression of CLDN2 in podocytes is associated with childhood onset nephrotic syndrome.Pediatr Res. 2019 Oct;86(4):485-491. doi: 10.1038/s41390-019-0423-7. Epub 2019 May 13.
17 Ephrin-A1 inhibits NSCLC tumor growth via induction of Cdx-2 a tumor suppressor gene.BMC Cancer. 2012 Jul 23;12:309. doi: 10.1186/1471-2407-12-309.
18 Down-regulation of Claudin-2 Expression and Proliferation by Epigenetic Inhibitors in Human Lung Adenocarcinoma A549 Cells.J Biol Chem. 2017 Feb 10;292(6):2411-2421. doi: 10.1074/jbc.M116.762807. Epub 2017 Jan 5.
19 Salmonella infection upregulates the leaky protein claudin-2 in intestinal epithelial cells.PLoS One. 2013;8(3):e58606. doi: 10.1371/journal.pone.0058606. Epub 2013 Mar 11.
20 Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus.J Neurogastroenterol Motil. 2018 Jan 30;24(1):147-158. doi: 10.5056/jnm17012.
21 The Use of Biomarkers and Genetic Screening to Diagnose Frontotemporal Dementia: Evidence and Clinical Implications.Front Neurosci. 2019 Aug 6;13:757. doi: 10.3389/fnins.2019.00757. eCollection 2019.
22 Effects of PRSS1-PRSS2 rs10273639, CLDN2 rs7057398 and MORC4 rs12688220 polymorphisms on individual susceptibility to pancreatitis: A meta-analysis.Genomics. 2020 Jan;112(1):848-852. doi: 10.1016/j.ygeno.2019.05.025. Epub 2019 Jun 1.
23 Identification of a missense variant in CLDN2 in obstructive azoospermia. J Hum Genet. 2019 Oct;64(10):1023-1032. doi: 10.1038/s10038-019-0642-0. Epub 2019 Jul 18.
24 CLDN2 inhibits the metastasis of osteosarcoma cells via down-regulating the afadin/ERK signaling pathway.Cancer Cell Int. 2018 Oct 17;18:160. doi: 10.1186/s12935-018-0662-4. eCollection 2018.
25 Homoectoine Protects Against Colitis by Preventing a Claudin Switch in Epithelial Tight Junctions.Dig Dis Sci. 2019 Feb;64(2):409-420. doi: 10.1007/s10620-018-5309-8. Epub 2018 Sep 29.
26 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
27 Claudin-2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function.J Cutan Pathol. 2014 Aug;41(8):630-9. doi: 10.1111/cup.12332. Epub 2014 Jul 4.
28 Spi-B-Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors.Cancer Res. 2017 Sep 15;77(18):4809-4822. doi: 10.1158/0008-5472.CAN-17-0020. Epub 2017 Jul 28.
29 Cell confluence regulates claudin-2 expression: possible role for ZO-1 and Rac.Am J Physiol Cell Physiol. 2018 Mar 1;314(3):C366-C378. doi: 10.1152/ajpcell.00234.2017. Epub 2017 Nov 29.
30 Differences in the expression profiles of claudin proteins in human nasopharyngeal carcinoma compared with non-neoplastic mucosa.Diagn Pathol. 2018 Feb 5;13(1):11. doi: 10.1186/s13000-018-0685-0.
31 Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia.Clin Nutr. 2017 Dec;36(6):1549-1557. doi: 10.1016/j.clnu.2016.09.025. Epub 2016 Oct 1.
32 Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
33 Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
34 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
35 Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9. Jpn J Ophthalmol. 2008 May-Jun;52(3):195-203. doi: 10.1007/s10384-008-0524-z. Epub 2008 Jul 27.
36 Induction of intestinalization in human esophageal keratinocytes is a multistep process. Carcinogenesis. 2009 Jan;30(1):122-30. doi: 10.1093/carcin/bgn227. Epub 2008 Oct 8.
37 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
38 Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer. Biochem Pharmacol. 2015 Nov 1;98(1):51-68. doi: 10.1016/j.bcp.2015.08.105. Epub 2015 Aug 24.
39 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.
40 Effects of residual levels of tetracycline on the barrier functions of human intestinal epithelial cells. Food Chem Toxicol. 2017 Nov;109(Pt 1):253-263. doi: 10.1016/j.fct.2017.09.004. Epub 2017 Sep 4.
41 Anti-invasive activity of sanguinarine through modulation of tight junctions and matrix metalloproteinase activities in MDA-MB-231 human breast carcinoma cells. Chem Biol Interact. 2009 May 15;179(2-3):185-91. doi: 10.1016/j.cbi.2008.11.009. Epub 2008 Nov 21.
42 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43 Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-B pathway. Chem Biol Interact. 2023 Jul 1;379:110520. doi: 10.1016/j.cbi.2023.110520. Epub 2023 Apr 28.
44 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
45 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.
46 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
47 Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway. Cancer Prev Res (Phila). 2009 Nov;2(11):942-50. doi: 10.1158/1940-6207.CAPR-08-0232. Epub 2009 Oct 27.
48 The marine biotoxin okadaic acid affects intestinal tight junction proteins in human intestinal cells. Toxicol In Vitro. 2019 Aug;58:150-160. doi: 10.1016/j.tiv.2019.03.033. Epub 2019 Mar 26.
49 Caffeic acid phenethyl ester down-regulates claudin-2 expression at the transcriptional and post-translational levels and enhances chemosensitivity to doxorubicin in lung adenocarcinoma A549 cells. J Nutr Biochem. 2018 Jun;56:205-214. doi: 10.1016/j.jnutbio.2018.02.016. Epub 2018 Mar 2.