Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUX60YO)

DOT Name Claudin-5 (CLDN5)
Synonyms Transmembrane protein deleted in VCFS; TMDVCF
Gene Name CLDN5
Related Disease
Myocardial infarction ( )
Nervous system inflammation ( )
Acute leukaemia ( )
Advanced cancer ( )
Alzheimer disease ( )
Amyloidosis ( )
Autism spectrum disorder ( )
B-cell neoplasm ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Cerebral infarction ( )
Chronic inflammatory demyelinating polyneuropathy ( )
Coeliac disease ( )
Colitis ( )
Crohn disease ( )
Dementia ( )
Depression ( )
Dilated cardiomyopathy 1A ( )
Endometriosis ( )
Glioblastoma multiforme ( )
Leukemia ( )
Lung squamous cell carcinoma ( )
Mental disorder ( )
Multiple sclerosis ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
Schizophrenia ( )
Sjogren syndrome ( )
Stroke ( )
Subarachnoid hemorrhage ( )
Transitional cell carcinoma ( )
Chronic obstructive pulmonary disease ( )
Glioma ( )
Huntington disease ( )
Meningioma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Squamous cell carcinoma ( )
Adult glioblastoma ( )
Amyotrophic lateral sclerosis ( )
Glaucoma/ocular hypertension ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Psychotic disorder ( )
UniProt ID
CLD5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00822
Sequence
MGSAALEILGLVLCLVGWGGLILACGLPMWQVTAFLDHNIVTAQTTWKGLWMSCVVQSTG
HMQCKVYDSVLALSTEVQAARALTVSAVLLAFVALFVTLAGAQCTTCVAPGPAKARVALT
GGVLYLFCGLLALVPLCWFANIVVREFYDPSVPVSQKYELGAALYIGWAATALLMVGGCL
LCCGAWVCTGRPDLSFPVKYSAPRRPTATGDYDKKNYV
Function Plays a major role in tight junction-specific obliteration of the intercellular space.
KEGG Pathway
Cell adhesion molecules (hsa04514 )
Tight junction (hsa04530 )
Leukocyte transendothelial migration (hsa04670 )
Pathogenic Escherichia coli infection (hsa05130 )
Hepatitis C (hsa05160 )
Reactome Pathway
RUNX1 regulates expression of components of tight junctions (R-HSA-8935964 )
Tight junction interactions (R-HSA-420029 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Myocardial infarction DIS655KI Definitive Biomarker [1]
Nervous system inflammation DISB3X5A Definitive Biomarker [2]
Acute leukaemia DISDQFDI Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Amyloidosis DISHTAI2 Strong Biomarker [6]
Autism spectrum disorder DISXK8NV Strong Biomarker [7]
B-cell neoplasm DISVY326 Strong Altered Expression [8]
Brain neoplasm DISY3EKS Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Altered Expression [10]
Breast carcinoma DIS2UE88 Strong Altered Expression [10]
Cerebral infarction DISR1WNP Strong Biomarker [11]
Chronic inflammatory demyelinating polyneuropathy DISNGBLD Strong Altered Expression [12]
Coeliac disease DISIY60C Strong Genetic Variation [13]
Colitis DISAF7DD Strong Altered Expression [14]
Crohn disease DIS2C5Q8 Strong Altered Expression [15]
Dementia DISXL1WY Strong Altered Expression [16]
Depression DIS3XJ69 Strong Biomarker [17]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [18]
Endometriosis DISX1AG8 Strong Altered Expression [19]
Glioblastoma multiforme DISK8246 Strong Altered Expression [20]
Leukemia DISNAKFL Strong Altered Expression [21]
Lung squamous cell carcinoma DISXPIBD Strong Biomarker [22]
Mental disorder DIS3J5R8 Strong Biomarker [17]
Multiple sclerosis DISB2WZI Strong Biomarker [17]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [23]
Pancreatic cancer DISJC981 Strong Biomarker [24]
Schizophrenia DISSRV2N Strong Biomarker [17]
Sjogren syndrome DISUBX7H Strong Altered Expression [25]
Stroke DISX6UHX Strong Altered Expression [26]
Subarachnoid hemorrhage DISI7I8Y Strong Biomarker [27]
Transitional cell carcinoma DISWVVDR Strong Altered Expression [28]
Chronic obstructive pulmonary disease DISQCIRF moderate Altered Expression [29]
Glioma DIS5RPEH moderate Altered Expression [30]
Huntington disease DISQPLA4 moderate Altered Expression [31]
Meningioma DISPT4TG moderate Biomarker [32]
Prostate cancer DISF190Y moderate Biomarker [33]
Prostate carcinoma DISMJPLE moderate Biomarker [33]
Squamous cell carcinoma DISQVIFL moderate Altered Expression [34]
Adult glioblastoma DISVP4LU Limited Altered Expression [20]
Amyotrophic lateral sclerosis DISF7HVM Limited Altered Expression [35]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [36]
Lung adenocarcinoma DISD51WR Limited Altered Expression [37]
Lung cancer DISCM4YA Limited Biomarker [37]
Lung carcinoma DISTR26C Limited Biomarker [37]
Metastatic malignant neoplasm DIS86UK6 Limited Altered Expression [38]
Neoplasm DISZKGEW Limited Biomarker [20]
Psychotic disorder DIS4UQOT Limited Biomarker [39]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Claudin-5 (CLDN5). [40]
Progesterone DMUY35B Approved Progesterone increases the expression of Claudin-5 (CLDN5). [41]
Sanguinarine DMDINFS Approved Sanguinarine decreases the expression of Claudin-5 (CLDN5). [42]
Guanfacine extended release DMB1CZ8 Approved Guanfacine extended release decreases the expression of Claudin-5 (CLDN5). [43]
Glycine DMIOZ29 Approved Glycine decreases the expression of Claudin-5 (CLDN5). [44]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Claudin-5 (CLDN5). [45]
CS-600G DM1PV4Y Phase 3 CS-600G increases the expression of Claudin-5 (CLDN5). [46]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Claudin-5 (CLDN5). [47]
LY294002 DMY1AFS Phase 1 LY294002 decreases the expression of Claudin-5 (CLDN5). [48]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Claudin-5 (CLDN5). [49]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Claudin-5 (CLDN5). [44]
acrolein DMAMCSR Investigative acrolein decreases the expression of Claudin-5 (CLDN5). [50]
U0126 DM31OGF Investigative U0126 increases the expression of Claudin-5 (CLDN5). [46]
Lead acetate DML0GZ2 Investigative Lead acetate decreases the expression of Claudin-5 (CLDN5). [51]
Phenanthrene-9,10-dione DMG8KS9 Investigative Phenanthrene-9,10-dione decreases the expression of Claudin-5 (CLDN5). [52]
JWH-133 DM1DEYU Investigative JWH-133 increases the expression of Claudin-5 (CLDN5). [53]
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⏷ Show the Full List of 16 Drug(s)

References

1 Altered detection of molecules associated with leukocyte traffic in HUVECs derived from newborns with a strong family history of myocardial infarction.Acta Histochem. 2008;110(1):42-52. doi: 10.1016/j.acthis.2007.05.007. Epub 2007 Aug 31.
2 AKT2 maintains brain endothelial claudin-5 expression and selective activation of IR/AKT2/FOXO1-signaling reverses barrier dysfunction.J Cereb Blood Flow Metab. 2020 Feb;40(2):374-391. doi: 10.1177/0271678X18817512. Epub 2018 Dec 21.
3 Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins.PLoS One. 2011;6(8):e20599. doi: 10.1371/journal.pone.0020599. Epub 2011 Aug 17.
4 Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases.Pathol Oncol Res. 2017 Apr;23(2):245-252. doi: 10.1007/s12253-016-0084-3. Epub 2016 Jul 9.
5 The role of LINC00094/miR-224-5p (miR-497-5p)/Endophilin-1 axis in Memantine mediated protective effects on blood-brain barrier in AD microenvironment.J Cell Mol Med. 2019 May;23(5):3280-3292. doi: 10.1111/jcmm.14214. Epub 2019 Feb 22.
6 Adiponectin controls the apoptosis and the expression of tight junction proteins in brain endothelial cells through AdipoR1 under beta amyloid toxicity.Cell Death Dis. 2017 Oct 12;8(10):e3102. doi: 10.1038/cddis.2017.491.
7 Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.Mol Autism. 2016 Nov 29;7:49. doi: 10.1186/s13229-016-0110-z. eCollection 2016.
8 Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion.Neural Regen Res. 2019 May;14(5):783-793. doi: 10.4103/1673-5374.249226.
9 CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating bloodbrain barrier permeability in tumor brain metastasis.Oncol Rep. 2018 Mar;39(3):1441-1453. doi: 10.3892/or.2018.6208. Epub 2018 Jan 10.
10 Claudin-5 is involved in breast cancer cell motility through the N-WASP and ROCK signalling pathways.J Exp Clin Cancer Res. 2012 May 4;31(1):43. doi: 10.1186/1756-9966-31-43.
11 Absence of MCP-induced Protein 1 Enhances Blood-Brain Barrier Breakdown after Experimental Stroke in Mice.Int J Mol Sci. 2019 Jun 30;20(13):3214. doi: 10.3390/ijms20133214.
12 Fingolimod promotes blood-nerve barrier properties in vitro.Brain Behav. 2018 Mar 25;8(4):e00924. doi: 10.1002/brb3.924. eCollection 2018 Apr.
13 Gene, gut and schizophrenia: the meeting point for the gene-environment interaction in developing schizophrenia.Med Hypotheses. 2005;64(3):547-52. doi: 10.1016/j.mehy.2004.08.011.
14 Cortical Inflammation is Increased in a DSS-Induced Colitis Mouse Model.Neurosci Bull. 2018 Dec;34(6):1058-1066. doi: 10.1007/s12264-018-0288-5. Epub 2018 Sep 17.
15 Gut Barrier Dysfunction-A Primary Defect in Twins with Crohn's Disease Predominantly Caused by Genetic Predisposition.J Crohns Colitis. 2018 Nov 9;12(10):1200-1209. doi: 10.1093/ecco-jcc/jjy045.
16 STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier.Blood. 2008 Feb 15;111(4):2062-72. doi: 10.1182/blood-2007-05-091207. Epub 2007 Nov 14.
17 Claudin-5: gatekeeper of neurological function.Fluids Barriers CNS. 2019 Jan 29;16(1):3. doi: 10.1186/s12987-019-0123-z.
18 Detection of differentially methylated gene promoters in failing and nonfailing human left ventricle myocardium using computation analysis.Physiol Genomics. 2013 Jul 15;45(14):597-605. doi: 10.1152/physiolgenomics.00013.2013. Epub 2013 May 21.
19 Differential expression of claudins in human endometrium and endometriosis.Gynecol Endocrinol. 2008 Aug;24(8):442-9. doi: 10.1080/09513590802242694.
20 TLR-4/Wnt modulation as new therapeutic strategy in the treatment of glioblastomas.Oncotarget. 2018 Dec 25;9(101):37564-37580. doi: 10.18632/oncotarget.26500. eCollection 2018 Dec 25.
21 Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.Hematol Oncol. 2017 Sep;35(3):365-373. doi: 10.1002/hon.2289. Epub 2016 Mar 21.
22 Claudin-5, -7, and -18 suppress proliferation mediated by inhibition of phosphorylation of Akt in human lung squamous cell carcinoma.Biochim Biophys Acta Mol Cell Res. 2017 Feb;1864(2):293-302. doi: 10.1016/j.bbamcr.2016.11.018. Epub 2016 Nov 21.
23 Targeting claudin-overexpressing thyroid and lung cancer by modified Clostridiumperfringens enterotoxin.Mol Oncol. 2020 Feb;14(2):261-276. doi: 10.1002/1878-0261.12615. Epub 2020 Jan 8.
24 Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays.Cancer Res. 2003 Jul 1;63(13):3735-42.
25 Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells.J Biol Chem. 2002 May 24;277(21):18528-34. doi: 10.1074/jbc.M200592200. Epub 2002 Mar 13.
26 Mice deficient in endothelial 5 integrin are profoundly resistant to experimental ischemic stroke.J Cereb Blood Flow Metab. 2017 Jan;37(1):85-96. doi: 10.1177/0271678X15616979. Epub 2015 Nov 13.
27 Mitoquinone attenuates blood-brain barrier disruption through Nrf2/PHB2/OPA1 pathway after subarachnoid hemorrhage in rats.Exp Neurol. 2019 Jul;317:1-9. doi: 10.1016/j.expneurol.2019.02.009. Epub 2019 Feb 16.
28 MiR-30a-5p Inhibits Epithelial-to-Mesenchymal Transition and Upregulates Expression of Tight Junction Protein Claudin-5 in Human Upper Tract Urothelial Carcinoma Cells.Int J Mol Sci. 2017 Aug 22;18(8):1826. doi: 10.3390/ijms18081826.
29 Impact of the Endothelial Tight Junction Protein Claudin-5 on Clinical Profiles of Patients With COPD.Allergy Asthma Immunol Res. 2018 Sep;10(5):533-542. doi: 10.4168/aair.2018.10.5.533.
30 Suppression of Angiotensin-(1-7) on the Disruption of Blood-Brain Barrier in Rat of Brain Glioma.Pathol Oncol Res. 2019 Jan;25(1):429-435. doi: 10.1007/s12253-018-0471-z. Epub 2018 Sep 18.
31 Comparative transcriptomics of choroid plexus in Alzheimer's disease, frontotemporal dementia and Huntington's disease: implications for CSF homeostasis.Fluids Barriers CNS. 2018 May 31;15(1):18. doi: 10.1186/s12987-018-0102-9.
32 Modulation of Dkk-3 and claudin-5 as new therapeutic strategy in the treatment of meningiomas.Oncotarget. 2017 Aug 7;8(40):68280-68290. doi: 10.18632/oncotarget.20047. eCollection 2017 Sep 15.
33 Prognostic potential of ERG (ETS-related gene) expression in prostatic adenocarcinoma.Int Urol Nephrol. 2013 Jun;45(3):727-33. doi: 10.1007/s11255-013-0406-2. Epub 2013 May 18.
34 Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas.Mod Pathol. 2007 Sep;20(9):947-54. doi: 10.1038/modpathol.3800835. Epub 2007 Jun 22.
35 ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration.Nat Neurosci. 2008 Apr;11(4):420-2. doi: 10.1038/nn2073. Epub 2008 Mar 16.
36 Ocular manifestations of 22q11.2 microduplication.Ophthalmology. 2014 Jan;121(1):392-398. doi: 10.1016/j.ophtha.2013.06.040. Epub 2013 Aug 21.
37 Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis.CNS Neurosci Ther. 2017 Dec;23(12):947-960. doi: 10.1111/cns.12764. Epub 2017 Sep 29.
38 Effect of bevacizumab on the tight junction proteins of vascular endothelial cells.Am J Transl Res. 2019 Sep 15;11(9):5546-5559. eCollection 2019.
39 Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia.Mol Psychiatry. 2018 Nov;23(11):2156-2166. doi: 10.1038/mp.2017.156. Epub 2017 Oct 10.
40 Arsenic downregulates tight junction claudin proteins through p38 and NF-B in intestinal epithelial cell line, HT-29. Toxicology. 2017 Mar 15;379:31-39. doi: 10.1016/j.tox.2017.01.011. Epub 2017 Jan 20.
41 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
42 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.
43 Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Controlled Trial. Inflamm Bowel Dis. 2019 May 4;25(6):1006-1018. doi: 10.1093/ibd/izz017.
44 Effects of glyphosate and aminomethylphosphonic acid on an isogeneic model of the human blood-brain barrier. Toxicol Lett. 2019 Apr;304:39-49. doi: 10.1016/j.toxlet.2018.12.013. Epub 2018 Dec 31.
45 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
46 Loxoprofen enhances intestinal barrier function via generation of its active metabolite by carbonyl reductase 1 in differentiated Caco-2?cells. Chem Biol Interact. 2021 Oct 1;348:109634. doi: 10.1016/j.cbi.2021.109634. Epub 2021 Sep 8.
47 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
48 Involvement of claudin-5 in H(2)S-induced acute lung injury. J Toxicol Sci. 2020;45(5):293-304. doi: 10.2131/jts.45.293.
49 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
50 Endothelial dysfunction and claudin 5 regulation during acrolein-induced lung injury. Am J Respir Cell Mol Biol. 2011 Apr;44(4):483-90. doi: 10.1165/rcmb.2009-0391OC. Epub 2010 Jun 4.
51 [Changes and regulatory mechanism of tight junction proteins in in vitro model of lead-induced blood-brain barrier injury]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013 Nov;29(11):1141-6.
52 9,10-Phenanthrenequinone provokes dysfunction of brain endothelial barrier through down-regulating expression of claudin-5. Toxicology. 2021 Sep;461:152896. doi: 10.1016/j.tox.2021.152896. Epub 2021 Aug 12.
53 Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. J Neurosci. 2012 Mar 21;32(12):4004-16. doi: 10.1523/JNEUROSCI.4628-11.2012.