Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK3D5WP)

• DOT Name: Cadherin-10 (CDH10)
• Synonyms: T2-cadherin
• Gene Name: CDH10
• Related Disease:
  Adenocarcinoma
  Alcohol dependence
  Autism
  Autism spectrum disorder
  Colorectal carcinoma
  Familial adenomatous polyposis
  Familial pancreatic carcinoma
  Matthew-Wood syndrome
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Congenital heart disease
• UniProt ID: CAD10_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MTIHQFLLLFLFWVCLPHFCSPEIMFRRTPVPQQRILSSRVPRSDGKILHRQKRGWMWNQ
  FFLLEEYTGSDYQYVGKLHSDQDKGDGSLKYILSGDGAGTLFIIDEKTGDIHATRRIDRE
  EKAFYTLRAQAINRRTLRPVEPESEFVIKIHDINDNEPTFPEEIYTASVPEMSVVGTSVV
  QVTATDADDPSYGNSARVIYSILQGQPYFSVEPETGIIRTALPNMNRENREQYQVVIQAK
  DMGGQMGGLSGTTTVNITLTDVNDNPPRFPQNTIHLRVLESSPVGTAIGSVKATDADTGK
  NAEVEYRIIDGDGTDMFDIVTEKDTQEGIITVKKPLDYESRRLYTLKVEAENTHVDPRFY
  YLGPFKDTTIVKISIEDVDEPPVFSRSSYLFEVHEDIEVGTIIGTVMARDPDSISSPIRF
  SLDRHTDLDRIFNIHSGNGSLYTSKPLDRELSQWHNLTVIAAEINNPKETTRVAVFVRIL
  DVNDNAPQFAVFYDTFVCENARPGQLIQTISAVDKDDPLGGQKFFFSLAAVNPNFTVQDN
  EDNTARILTRKNGFNRHEISTYLLPVVISDNDYPIQSSTGTLTIRVCACDSQGNMQSCSA
  EALLLPAGLSTGALIAILLCIIILLVIVVLFAALKRQRKKEPLILSKEDIRDNIVSYNDE
  GGGEEDTQAFDIGTLRNPAAIEEKKLRRDIIPETLFIPRRTPTAPDNTDVRDFINERLKE
  HDLDPTAPPYDSLATYAYEGNDSIAESLSSLESGTTEGDQNYDYLREWGPRFNKLAEMYG
  GGESDKDS
• Function: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
• Tissue Specificity: Predominantly expressed in brain. Also found in adult and fetal kidney. Very low levels detected in prostate and fetal lung.
• Reactome Pathway: Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[1]
Familial pancreatic carcinoma	DIS1XROR	Strong	Genetic Variation	[1]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[6]
Congenital heart disease	DISQBA23	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cadherin-10 (CDH10).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cadherin-10 (CDH10).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cadherin-10 (CDH10).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cadherin-10 (CDH10).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cadherin-10 (CDH10).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cadherin-10 (CDH10).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cadherin-10 (CDH10).	[14]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cadherin-10 (CDH10).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cadherin-10 (CDH10).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cadherin-10 (CDH10).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cadherin-10 (CDH10).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cadherin-10 (CDH10).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cadherin-10 (CDH10).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Cadherin-10 (CDH10).	[20]

References

• [1] Alterations of type II classical cadherin, cadherin-10 (CDH10), is associated with pancreatic ductal adenocarcinomas.Genes Chromosomes Cancer. 2017 May;56(5):427-435. doi: 10.1002/gcc.22447. Epub 2017 Mar 7.
• [2] Cadherins and neuropsychiatric disorders.Brain Res. 2012 Aug 27;1470:130-44. doi: 10.1016/j.brainres.2012.06.020. Epub 2012 Jul 2.
• [3] Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with Synaptic Proteins.J Neurosci. 2017 Nov 15;37(46):11127-11139. doi: 10.1523/JNEUROSCI.1153-17.2017. Epub 2017 Oct 13.
• [4] Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.
• [5] Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer.Gut. 2015 Apr;64(4):636-45. doi: 10.1136/gutjnl-2013-306620. Epub 2014 Jun 20.
• [6] Gene panel model predictive of outcome in men at high-risk of systemic progression and death from prostate cancer after radical retropubic prostatectomy.J Clin Oncol. 2008 Aug 20;26(24):3930-6. doi: 10.1200/JCO.2007.15.6752.
• [7] Prenatal diagnosis of a familial 5p14.3-p14.1 deletion encompassing CDH18, CDH12, PMCHL1, PRDM9 and CDH10 in a fetus with congenital heart disease on prenatal ultrasound.Taiwan J Obstet Gynecol. 2018 Oct;57(5):734-738. doi: 10.1016/j.tjog.2018.08.023.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [16] 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.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] 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.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [20] 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.