Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC06P9H)

• DOT Name: Cadherin-18 (CDH18)
• Synonyms: Cadherin-14
• Gene Name: CDH18
• Related Disease:
  Alcohol dependence
  Glioma
  High blood pressure
  Leprosy
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: CAD18_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MKITSTSCICPVLVCLCFVQRCYGTAHHSSIKVMRNQTKHIEGETEVHHRPKRGWVWNQF
  FVLEEHMGPDPQYVGKLHSNSDKGDGSVKYILTGEGAGTIFIIDDTTGDIHSTKSLDREQ
  KTHYVLHAQAIDRRTNKPLEPESEFIIKVQDINDNAPKFTDGPYIVTVPEMSDMGTSVLQ
  VTATDADDPTYGNSARVVYSILQGQPYFSVDPKTGVIRTALHNMDREAREHYSVVIQAKD
  MAGQVGGLSGSTTVNITLTDVNDNPPRFPQKHYQLYVPESAQVGSAVGKIKANDADTGSN
  ADMTYSIINGDGMGIFSISTDKETREGILSLKKPLNYEKKKSYTLNIEGANTHLDFRFSH
  LGPFKDATMLKIIVGDVDEPPLFSMPSYLMEVYENAKIGTVVGTVLAQDPDSTNSLVRYF
  INYNVEDDRFFNIDANTGTIRTTKVLDREETPWYNITVTASEIDNPDLLSHVTVGIRVLD
  VNDNPPELAREYDIIVCENSKPGQVIHTISATDKDDFANGPRFNFFLDERLPVNPNFTLK
  DNEDNTASILTRRRRFSRTVQDVYYLPIMISDGGIPSLSSSSTLTIRVCACERDGRVRTC
  HAEAFLSSAGLSTGALIAILLCVLILLAIVVLFITLRRSKKEPLIISEEDVRENVVTYDD
  EGGGEEDTEAFDITALRNPSAAEELKYRRDIRPEVKLTPRHQTSSTLESIDVQEFIKQRL
  AEADLDPSVPPYDSLQTYAYEGQRSEAGSISSLDSATTQSDQDYHYLGDWGPEFKKLAEL
  YGEIESERTT
• 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.
• Reactome Pathway: Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[3]
Leprosy	DISAA4UI	moderate	Genetic Variation	[4]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[5]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[5]

9 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 Cadherin-18 (CDH18).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cadherin-18 (CDH18).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cadherin-18 (CDH18).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cadherin-18 (CDH18).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cadherin-18 (CDH18).	[9]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Cadherin-18 (CDH18).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cadherin-18 (CDH18).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Cadherin-18 (CDH18).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cadherin-18 (CDH18).	[13]

2 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 Cadherin-18 (CDH18).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Cadherin-18 (CDH18).	[12]

References

• [1] Cadherins and neuropsychiatric disorders.Brain Res. 2012 Aug 27;1470:130-44. doi: 10.1016/j.brainres.2012.06.020. Epub 2012 Jul 2.
• [2] A Novel Tumor-Suppressor, CDH18, Inhibits Glioma Cell Invasiveness Via UQCRC2 and Correlates with the Prognosis of Glioma Patients.Cell Physiol Biochem. 2018;48(4):1755-1770. doi: 10.1159/000492317. Epub 2018 Aug 3.
• [3] Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.PLoS Genet. 2017 May 12;13(5):e1006728. doi: 10.1371/journal.pgen.1006728. eCollection 2017 May.
• [4] Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.Nat Genet. 2015 Mar;47(3):267-71. doi: 10.1038/ng.3212. Epub 2015 Feb 2.
• [5] Integrated analysis of gene expression and copy number variations in MET protooncogenetransformed human primary osteoblasts.Mol Med Rep. 2018 Feb;17(2):2543-2548. doi: 10.3892/mmr.2017.8135. Epub 2017 Nov 22.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Estrogen-responsive genes newly found to be modified by TCDD exposure in human cell lines and mouse systems. Mol Cell Endocrinol. 2007 Jun 30;272(1-2):38-49.
• [9] 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.
• [10] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [11] 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.
• [12] 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.
• [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.