Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV9N5XK)

• DOT Name: Cadherin-9 (CDH9)
• Gene Name: CDH9
• Related Disease:
  Acute leukaemia
  Alcohol dependence
  Anorexia nervosa cachexia
  Autism
  Autism spectrum disorder
  Clear cell renal carcinoma
  Dental caries
  Major depressive disorder
  Obsessive compulsive disorder
  Renal cell carcinoma
  Renal fibrosis
  Metastatic malignant neoplasm
• UniProt ID: CADH9_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MRTYHYIPLFIWTYMFHTVDTILLQEKPNSYLSSKKIAGLTKDDGKMLRRTKRGWMWNQF
  FLLEEYTGTDTQYVGKLHTDQDKGDGNLKYILTGDGAGSLFVIDENTGDIHAAKKLDREE
  KSLYILRAKAIDRKTGRQVEPESEFIIKIHDINDNEPKFTKDLYTASVPEMSGVGTSVIQ
  VTATDADDANYGNSAKVVYSILQGQPYFSVDPESGIIKTALPDMSRENREQYQVVIQAKD
  MGGQMGGLSGTTTVNITLTDVNNNPPRFPQSTYQFNSPESVPLGTHLGRIKANDPDVGEN
  AEMEYSIAEGDGADMFDVITDKDTQEGIITVKQNLDFENQMLYTLRVDASNTHPDPRFLH
  LGPFKDTAVVKISVEDIDEPPVFTKVSYLIEVDEDVKEGSIIGQVTAYDPDARNNLIKYS
  VDRHTDMDRIFGIHSENGSIFTLKALDRESSPWHNITVTATEINNPKQSSHIPVFIRILD
  INDHAPEFAMYYETFVCENAKPGQLIQTVSVMDKDDPPRGHKFFFEPVPEFTLNPNFTIV
  DNKDNTAGIMTRKDGYSRNKMSTYLLPILIFDNDYPIQSSTGTLTIRVCACDNQGNMQSC
  TAEALILSAGLSTGALVAILLCVLILLILVVLFAALKRQRKKEPLIISKDDVRDNIVTYN
  DEGGGEEDTQAFDIGTLRNPEAREDSKLRRDVMPETIFQIRRTVPLWENIDVQDFIHRRL
  KENDADPSAPPYDSLATYAYEGNDSIADSLSSLESLTADCNQDYDYLSDWGPRFKKLADM
  YGGDDSDRD
• 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

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[1]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[2]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Genetic Variation	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[5]
Dental caries	DISRBCMD	Strong	Genetic Variation	[6]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[7]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[5]
Renal fibrosis	DISMHI3I	Strong	Altered Expression	[5]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[8]

3 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-9 (CDH9).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cadherin-9 (CDH9).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cadherin-9 (CDH9).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cadherin-9 (CDH9).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cadherin-9 (CDH9).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cadherin-9 (CDH9).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cadherin-9 (CDH9).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cadherin-9 (CDH9).	[11]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Cadherin-9 (CDH9).	[15]

References

• [1] Biparental inheritance of chromosomal abnormalities in male twins with non-syndromic mental retardation.Eur J Med Genet. 2011 Jul-Aug;54(4):e383-8. doi: 10.1016/j.ejmg.2011.03.008. Epub 2011 Mar 21.
• [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] Common genetic background in anorexia nervosa and obsessive compulsive disorder: preliminary results from an association study.J Psychiatr Res. 2013 Jun;47(6):747-54. doi: 10.1016/j.jpsychires.2012.12.015. Epub 2013 Jan 19.
• [4] Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum.Mol Brain. 2019 May 2;12(1):40. doi: 10.1186/s13041-019-0461-4.
• [5] Cadherin-9 is a novel cell surface marker for the heterogeneous pool of renal fibroblasts.PLoS One. 2007 Aug 1;2(7):e657. doi: 10.1371/journal.pone.0000657.
• [6] Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.Nat Commun. 2019 Jun 24;10(1):2773. doi: 10.1038/s41467-019-10630-1.
• [7] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [8] A signal-based method for finding driver modules of breast cancer metastasis to the lung.Sci Rep. 2017 Aug 30;7(1):10023. doi: 10.1038/s41598-017-09951-2.
• [9] 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.
• [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] 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.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] 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.
• [14] 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.
• [15] Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway. Cancer Prev Res (Phila). 2009 Nov;2(11):942-50. doi: 10.1158/1940-6207.CAPR-08-0232. Epub 2009 Oct 27.