Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEN8ID2)

• DOT Name: Claudin-6 (CLDN6)
• Synonyms: Skullin
• Gene Name: CLDN6
• UniProt ID: CLD6_HUMAN
• Pfam ID: PF00822
• Sequence:
  MASAGMQILGVVLTLLGWVNGLVSCALPMWKVTAFIGNSIVVAQVVWEGLWMSCVVQSTG
  QMQCKVYDSLLALPQDLQAARALCVIALLVALFGLLVYLAGAKCTTCVEEKDSKARLVLT
  SGIVFVISGVLTLIPVCWTAHAIIRDFYNPLVAEAQKRELGASLYLGWAASGLLLLGGGL
  LCCTCPSGGSQGPSHYMARYSTSAPAISRGPSEYPTKNYV
• Function: Plays a major role in tight junction-specific obliteration of the intercellular space; (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) entry into hepatic cells.
• Tissue Specificity: Expressed in the liver, in peripheral blood mononuclear cells and hepatocarcinoma cell lines.
• 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

3 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-6 (CLDN6).	[1]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Claudin-6 (CLDN6).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Claudin-6 (CLDN6).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Claudin-6 (CLDN6).	[2]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Claudin-6 (CLDN6).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Claudin-6 (CLDN6).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Claudin-6 (CLDN6).	[6]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Claudin-6 (CLDN6).	[2]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Claudin-6 (CLDN6).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Claudin-6 (CLDN6).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Claudin-6 (CLDN6).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Claudin-6 (CLDN6).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Claudin-6 (CLDN6).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Claudin-6 (CLDN6).	[2]

References

• [1] 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.
• [2] 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.
• [3] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [4] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] 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.