Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNN6UTL)

DOT Name	Claudin-11 (CLDN11)
Synonyms	Oligodendrocyte-specific protein
Gene Name	CLDN11
Related Disease	Bone disease ( ) Coagulation defect ( ) Colorectal carcinoma ( ) Endometriosis ( ) Epithelial ovarian cancer ( ) Gastric cancer ( ) Hepatocellular carcinoma ( ) Herpes simplex infection ( ) Leukodystrophy, hypomyelinating, 22 ( ) Lung squamous cell carcinoma ( ) Medulloblastoma ( ) Neoplasm ( ) Nervous system inflammation ( ) Oligospermia ( ) Optic neuritis ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Staphylococcus aureus infection ( ) Stomach cancer ( ) Systemic lupus erythematosus ( ) Advanced cancer ( ) Laryngeal squamous cell carcinoma ( ) Mental disorder ( ) Psychotic disorder ( ) Actinic keratosis ( ) Cutaneous squamous cell carcinoma ( ) Hypothyroidism ( ) Keratosis ( ) Melanoma ( ) Multiple sclerosis ( ) Nasopharyngeal carcinoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Type-1/2 diabetes ( )
UniProt ID	CLD11_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00822
Sequence	MVATCLQVVGFVTSFVGWIGVIVTTSTNDWVVTCGYTIPTCRKLDELGSKGLWADCVMAT GLYHCKPLVDILILPGYVQACRALMIAASVLGLPAILLLLTVLPCIRMGQEPGVAKYRRA QLAGVLLILLALCALVATIWFPVCAHRETTIVSFGYSLYAGWIGAVLCLVGGCVILCCAG DAQAFGENRFYYTAGSSSPTHAKSAHV
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

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Bone disease	DISE1F82	Strong	Biomarker	[1]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Endometriosis	DISX1AG8	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[5]
Leukodystrophy, hypomyelinating, 22	DISCX0R5	Strong	Autosomal dominant	[8]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[9]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Nervous system inflammation	DISB3X5A	Strong	Altered Expression	[12]
Oligospermia	DIS6YJF3	Strong	Altered Expression	[13]
Optic neuritis	DISDYCHC	Strong	Biomarker	[14]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Staphylococcus aureus infection	DISK6PTH	Strong	Biomarker	[15]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[15]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[16]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Posttranslational Modification	[17]
Mental disorder	DIS3J5R8	moderate	Genetic Variation	[18]
Psychotic disorder	DIS4UQOT	moderate	Genetic Variation	[18]
Actinic keratosis	DISR1RC5	Limited	Biomarker	[19]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[19]
Hypothyroidism	DISR0H6D	Limited	Biomarker	[20]
Keratosis	DISF0NF1	Limited	Biomarker	[19]
Melanoma	DIS1RRCY	Limited	Biomarker	[21]
Multiple sclerosis	DISB2WZI	Limited	Altered Expression	[12]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Posttranslational Modification	[22]
Prostate cancer	DISF190Y	Limited	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[20]
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⏷ Show the Full List of 34 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Claudin-11 (CLDN11).	[24]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Claudin-11 (CLDN11).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Claudin-11 (CLDN11).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Claudin-11 (CLDN11).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Claudin-11 (CLDN11).	[38]
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11 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 Claudin-11 (CLDN11).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Claudin-11 (CLDN11).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Claudin-11 (CLDN11).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Claudin-11 (CLDN11).	[29]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Claudin-11 (CLDN11).	[30]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Claudin-11 (CLDN11).	[31]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Claudin-11 (CLDN11).	[32]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Claudin-11 (CLDN11).	[33]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Claudin-11 (CLDN11).	[34]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Claudin-11 (CLDN11).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Claudin-11 (CLDN11).	[39]
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⏷ Show the Full List of 11 Drug(s)

References

1	Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling.Exp Mol Med. 2018 Apr 27;50(4):1-18. doi: 10.1038/s12276-018-0076-3.
2	Impaired platelet function in a patient with P2Y12 deficiency caused by a mutation in the translation initiation codon.J Thromb Haemost. 2005 Oct;3(10):2315-23. doi: 10.1111/j.1538-7836.2005.01554.x.
3	Drugs Targeting Epigenetic Modifications and Plausible Therapeutic Strategies Against Colorectal Cancer.Front Pharmacol. 2019 Jun 6;10:588. doi: 10.3389/fphar.2019.00588. eCollection 2019.
4	Impaired Localization of Claudin-11 in Endometriotic Epithelial Cells Compared to Endometrial Cells.Reprod Sci. 2019 Sep;26(9):1181-1192. doi: 10.1177/1933719118811643. Epub 2018 Dec 4.
5	Ovarian epithelial cell lineage-specific gene expression using the promoter of a retrovirus-like element.Cancer Res. 2001 Feb 15;61(4):1291-5.
6	Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.PLoS One. 2017 Mar 28;12(3):e0174476. doi: 10.1371/journal.pone.0174476. eCollection 2017.
7	miR-99b promotes metastasis of hepatocellular carcinoma through inhibition of claudin11 expression and may serve as a prognostic marker.Oncol Rep. 2015 Sep;34(3):1415-23. doi: 10.3892/or.2015.4104. Epub 2015 Jul 2.
8	De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy. Brain. 2021 Mar 3;144(2):411-419. doi: 10.1093/brain/awaa410.
9	Chrysin enhances anticancer drug-induced toxicity mediated by the reduction of claudin-1 and 11 expression in a spheroid culture model of lung squamous cell carcinoma cells.Sci Rep. 2019 Sep 24;9(1):13753. doi: 10.1038/s41598-019-50276-z.
10	Silencing of E3 Ubiquitin Ligase RNF8 Enhances Ionizing Radiation Sensitivity of Medulloblastoma Cells by Promoting the Deubiquitination of PCNA.Oncol Res. 2018 Oct 17;26(9):1365-1373. doi: 10.3727/096504018X15154085345907. Epub 2018 Jan 10.
11	Snail-induced claudin-11 prompts collective migration for tumour progression.Nat Cell Biol. 2019 Feb;21(2):251-262. doi: 10.1038/s41556-018-0268-z. Epub 2019 Jan 21.
12	Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis.Mol Neurobiol. 2019 Mar;56(3):2039-2056. doi: 10.1007/s12035-018-1207-5. Epub 2018 Jul 8.
13	Claudin-11 expression increased in spermatogenic defect in human testes.Fertil Steril. 2011 Jan;95(1):385-8. doi: 10.1016/j.fertnstert.2010.08.023. Epub 2010 Sep 17.
14	Oligodendrocyte-specific protein is encephalitogenic in rhesus macaques and induces specific demyelination of the optic nerve.Eur J Immunol. 2008 May;38(5):1452-64. doi: 10.1002/eji.200737164.
15	An OMICS-based study of the role of C3dg in keratinocytes: RNA sequencing, antibody-chip array, and bioinformatics approaches.Int J Biol Macromol. 2019 Jul 15;133:391-411. doi: 10.1016/j.ijbiomac.2019.04.039. Epub 2019 Apr 8.
16	Promoter CpG island hypermethylation in dysplastic nevus and melanoma: CLDN11 as an epigenetic biomarker for malignancy.J Invest Dermatol. 2014 Dec;134(12):2957-2966. doi: 10.1038/jid.2014.270. Epub 2014 Jul 7.
17	The Clinical Signification of Claudin-11 Promoter Hypermethylation for Laryngeal Squamous Cell Carcinoma.Med Sci Monit. 2017 Jul 26;23:3635-3640. doi: 10.12659/msm.904751.
18	A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.Schizophr Res. 2010 Dec;124(1-3):192-9. doi: 10.1016/j.schres.2010.09.002.
19	Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38.Exp Dermatol. 2017 Sep;26(9):771-777. doi: 10.1111/exd.13278. Epub 2017 Apr 10.
20	Contemporaneous effects of diabetes mellitus and hypothyroidism on spermatogenesis and immunolocalization of Claudin-11 inside the seminiferous tubules of mice.BMC Dev Biol. 2018 Jun 26;18(1):15. doi: 10.1186/s12861-018-0174-4.
21	Promoter methylation as biomarkers for diagnosis of melanoma: A systematic review and meta-analysis.J Cell Physiol. 2019 May;234(5):7356-7367. doi: 10.1002/jcp.27495. Epub 2018 Oct 28.
22	Inactivation of the tight junction gene CLDN11 by aberrant hypermethylation modulates tubulins polymerization and promotes cell migration in nasopharyngeal carcinoma.J Exp Clin Cancer Res. 2018 May 10;37(1):102. doi: 10.1186/s13046-018-0754-y.
23	Novel pharmacologic targeting of tight junctions and focal adhesions in prostate cancer cells.PLoS One. 2014 Jan 31;9(1):e86238. doi: 10.1371/journal.pone.0086238. eCollection 2014.
24	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.
25	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
26	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
27	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
28	Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
29	Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
30	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
31	Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
32	Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
33	Expression of transcripts for myelin related genes in postmortem brain from cocaine abusers. Neurochem Res. 2009 Jan;34(1):46-54. doi: 10.1007/s11064-008-9655-3. Epub 2008 Mar 21.
34	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.
35	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
36	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.
37	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
38	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.
39	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.