Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5RV40)

• DOT Name: Claudin-23 (CLDN23)
• Gene Name: CLDN23
• Related Disease:
  Colorectal carcinoma
  Colonic neoplasm
  Gastric neoplasm
  Atopic dermatitis
• UniProt ID: CLD23_HUMAN
• Pfam ID: PF00822
• Sequence:
  MRTPVVMTLGMVLAPCGLLLNLTGTLAPGWRLVKGFLNQPVDVELYQGLWDMCREQSSRE
  RECGQTDQWGYFEAQPVLVARALMVTSLAATVLGLLLASLGVRCWQDEPNFVLAGLSGVV
  LFVAGLLGLIPVSWYNHFLGDRDVLPAPASPVTVQVSYSLVLGYLGSCLLLLGGFSLALS
  FAPWCDERCRRRRKGPSAGPRRSSVSTIQVEWPEPDLAPAIKYYSDGQHRPPPAQHRKPK
  PKPKVGFPMPRPRPKAYTNSVDVLDGEGWESQDAPSCSTHPCDSSLPCDSDL
• Function: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
• Tissue Specificity: Expressed in germinal center B-cells, placenta, stomach as well as in colon tumor.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Colonic neoplasm	DISSZ04P	Disputed	Altered Expression	[2]
Gastric neoplasm	DISOKN4Y	Disputed	Biomarker	[2]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[3]

2 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-23 (CLDN23).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Claudin-23 (CLDN23).	[12]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Claudin-23 (CLDN23).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Claudin-23 (CLDN23).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Claudin-23 (CLDN23).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Claudin-23 (CLDN23).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Claudin-23 (CLDN23).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Claudin-23 (CLDN23).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Claudin-23 (CLDN23).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Claudin-23 (CLDN23).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Claudin-23 (CLDN23).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Claudin-23 (CLDN23).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Claudin-23 (CLDN23).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Claudin-23 (CLDN23).	[14]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Claudin-23 (CLDN23).	[15]

References

• [1] Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer.Mol Med Rep. 2015 Jul;12(1):728-36. doi: 10.3892/mmr.2015.3378. Epub 2015 Feb 19.
• [2] CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family.Int J Mol Med. 2003 Jun;11(6):683-9.
• [3] Oral Janus kinase/SYK inhibition (ASN002) suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis.J Allergy Clin Immunol. 2019 Oct;144(4):1011-1024. doi: 10.1016/j.jaci.2019.07.013. Epub 2019 Jul 26.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial barrier and toxicity of ochratoxin A to Caco-2?cells. Food Chem Toxicol. 2019 Apr;126:25-33. doi: 10.1016/j.fct.2019.02.009. Epub 2019 Feb 11.
• [15] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.