Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2CVAKY)

• DOT Name: Claudin-10 (CLDN10)
• Synonyms: Oligodendrocyte-specific protein-like; OSP-like
• Gene Name: CLDN10
• Related Disease:
  Acute erythroid leukemia
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Bronchioalveolar carcinoma
  Cardiac failure
  Castration-resistant prostate carcinoma
  Congenital hydrocephalus
  Congestive heart failure
  Epithelial ovarian cancer
  HELIX syndrome
  Hepatocellular carcinoma
  Neoplasm
  Obesity
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Pheochromocytoma
  Primitive neuroectodermal tumor
  T-cell lymphoma
  Thyroid gland papillary carcinoma
  Disseminated intravascular coagulation
  Familial primary hypomagnesemia
  Lung adenocarcinoma
  Nephrocalcinosis
  T-cell acute lymphoblastic leukaemia
• UniProt ID: CLD10_HUMAN
• Pfam ID: PF00822
• Sequence:
  MASTASEIIAFMVSISGWVLVSSTLPTDYWKVSTIDGTVITTATYWANLWKACVTDSTGV
  SNCKDFPSMLALDGYIQACRGLMIAAVSLGFFGSIFALFGMKCTKVGGSDKAKAKIACLA
  GIVFILSGLCSMTGCSLYANKITTEFFDPLFVEQKYELGAALFIGWAGASLCIIGGVIFC
  FSISDNNKTPRYTYNGATSVMSSRTKYHGGEDFKTTNPSKQFDKNAYV
• Function: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Involved in the regulation of paracellular epithelia permeability to ions in multiple organs. It acts as a paracellular ion channel probably forming permselective pores; isoform 1 appears to create pores preferentially permeable to cations and isoform 2 for anions. In sweat glands and in the thick ascending limb (TAL) of Henle's loop in kidney, it controls paracellular sodium permeability which is essential for proper sweat production and renal function.
• Tissue Specificity: Expressed in the kidney, eccrine sweat glands and in all layers of the epidermis. In the kidney, it is detected in the thick ascending limb of Henle's loop (TAL) . In the sweat glands, it is expressed in cells from secretory portions, corresponding to the clear cells .
• 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

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Bronchioalveolar carcinoma	DISMLRZY	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[8]
Congenital hydrocephalus	DIS7O6UL	Strong	Genetic Variation	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
HELIX syndrome	DIS5HCN4	Strong	Autosomal recessive	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Obesity	DIS47Y1K	Strong	Biomarker	[14]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Pheochromocytoma	DIS56IFV	Strong	Biomarker	[15]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[16]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[17]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[12]
Disseminated intravascular coagulation	DISCAVOZ	moderate	Biomarker	[18]
Familial primary hypomagnesemia	DIS6TTKI	moderate	Biomarker	[19]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[20]
Nephrocalcinosis	DIS5ZVJP	moderate	Biomarker	[19]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Claudin-10 (CLDN10).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Claudin-10 (CLDN10).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Claudin-10 (CLDN10).	[24]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Claudin-10 (CLDN10).	[25]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Claudin-10 (CLDN10).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Claudin-10 (CLDN10).	[24]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Claudin-10 (CLDN10).	[27]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Claudin-10 (CLDN10).	[28]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Claudin-10 (CLDN10).	[29]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Claudin-10 (CLDN10).	[30]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Claudin-10 (CLDN10).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Claudin-10 (CLDN10).	[32]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Claudin-10 (CLDN10).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Claudin-10 (CLDN10).	[31]

References

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• [2] TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia.Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11416-20. doi: 10.1073/pnas.88.24.11416.
• [3] Inhibition of hepatocellular carcinoma invasion by suppression of claudin-10 in HLE cells.Mol Cancer Ther. 2007 Nov;6(11):2858-67. doi: 10.1158/1535-7163.MCT-07-0453.
• [4] CLDN10 promotes a malignant phenotype of osteosarcoma cells via JAK1/Stat1 signaling.J Cell Commun Signal. 2019 Sep;13(3):395-405. doi: 10.1007/s12079-019-00509-7. Epub 2019 Feb 22.
• [5] CLDN10 single nucleotide polymorphism rs1325774 alters the risk of breast cancer in south chinese women.Medicine (Baltimore). 2018 Dec;97(49):e13187. doi: 10.1097/MD.0000000000013187.
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• [9] The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus.Cell. 1998 Jun 12;93(6):985-96. doi: 10.1016/s0092-8674(00)81204-0.
• [10] Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer.Oncol Rep. 2017 May;37(5):3084-3092. doi: 10.3892/or.2017.5534. Epub 2017 Mar 27.
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• [14] Obesity is associated with shorter telomeres in 8 year-old children.Sci Rep. 2019 Dec 10;9(1):18739. doi: 10.1038/s41598-019-55283-8.
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• [16] Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors.Cancer Res. 1997 Aug 15;57(16):3526-31.
• [17] Mutation of inhibitory helix-loop-helix protein Id3 causes T-cell lymphoma in mice.Blood. 2010 Dec 16;116(25):5615-21. doi: 10.1182/blood-2010-03-274506. Epub 2010 Sep 17.
• [18] Therapeutic hypothermia for moderate and severe hypoxic ischaemic encephalopathy in newborns using low-cost devices - ice packs and phase changing material.Paediatr Int Child Health. 2019 Nov;39(4):234-239. doi: 10.1080/20469047.2018.1500805. Epub 2018 Aug 15.
• [19] Deletion of claudin-10 rescues claudin-16-deficient mice from hypomagnesemia and hypercalciuria.Kidney Int. 2018 Mar;93(3):580-588. doi: 10.1016/j.kint.2017.08.029. Epub 2017 Nov 10.
• [20] The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes.PLoS One. 2017 Nov 16;12(11):e0187333. doi: 10.1371/journal.pone.0187333. eCollection 2017.
• [21] T-cell acute lymphoblastic leukemia and the associated basic helix-loop-helix gene SCL/tal.Leuk Lymphoma. 1994 Jan;12(3-4):157-66. doi: 10.3109/10428199409059586.
• [22] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [23] 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.
• [24] 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.
• [25] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
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• [29] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.