Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF2HCGA)

• DOT Name: Cadherin-12 (CDH12)
• Synonyms: Brain cadherin; BR-cadherin; Neural type cadherin 2; N-cadherin 2
• Gene Name: CDH12
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate neoplasm
  Adenocarcinoma
• UniProt ID: CAD12_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MLTRNCLSLLLWVLFDGGLLTPLQPQPQQTLATEPRENVIHLPGQRSHFQRVKRGWVWNQ
  FFVLEEYVGSEPQYVGKLHSDLDKGEGTVKYTLSGDGAGTVFTIDETTGDIHAIRSLDRE
  EKPFYTLRAQAVDIETRKPLEPESEFIIKVQDINDNEPKFLDGPYVATVPEMSPVGAYVL
  QVKATDADDPTYGNSARVVYSILQGQPYFSIDPKTGVIRTALPNMDREVKEQYQVLIQAK
  DMGGQLGGLAGTTIVNITLTDVNDNPPRFPKSIFHLKVPESSPIGSAIGRIRAVDPDFGQ
  NAEIEYNIVPGDGGNLFDIVTDEDTQEGVIKLKKPLDFETKKAYTFKVEASNLHLDHRFH
  SAGPFKDTATVKISVLDVDEPPVFSKPLYTMEVYEDTPVGTIIGAVTAQDLDVGSSAVRY
  FIDWKSDGDSYFTIDGNEGTIATNELLDRESTAQYNFSIIASKVSNPLLTSKVNILINVL
  DVNEFPPEISVPYETAVCENAKPGQIIQIVSAADRDLSPAGQQFSFRLSPEAAIKPNFTV
  RDFRNNTAGIETRRNGYSRRQQELYFLPVVIEDSSYPVQSSTNTMTIRVCRCDSDGTILS
  CNVEAIFLPVGLSTGALIAILLCIVILLAIVVLYVALRRQKKKDTLMTSKEDIRDNVIHY
  DDEGGGEEDTQAFDIGALRNPKVIEENKIRRDIKPDSLCLPRQRPPMEDNTDIRDFIHQR
  LQENDVDPTAPPYDSLATYAYEGSGSVAESLSSIDSLTTEADQDYDYLTDWGPRFKVLAD
  MFGEEESYNPDKVT
• 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: Brain.
• Reactome Pathway: Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Cadherin-12 (CDH12) increases the Bone disorder ADR of Dexamethasone.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cadherin-12 (CDH12).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cadherin-12 (CDH12).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cadherin-12 (CDH12).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cadherin-12 (CDH12).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cadherin-12 (CDH12).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cadherin-12 (CDH12).	[12]

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 affects the methylation of Cadherin-12 (CDH12).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Cadherin-12 (CDH12).	[13]

References

• [1] Cadherin-12 enhances proliferation in colorectal cancer cells and increases progression by promoting EMT.Tumour Biol. 2016 Jul;37(7):9077-88. doi: 10.1007/s13277-015-4555-z. Epub 2016 Jan 14.
• [2] Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma.Pathol Oncol Res. 2018 Jan;24(1):35-43. doi: 10.1007/s12253-017-0194-6. Epub 2017 Feb 4.
• [3] The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma.Nat Genet. 2013 May;45(5):522-525. doi: 10.1038/ng.2583. Epub 2013 Mar 17.
• [4] Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.Nat Genet. 2018 May;50(5):682-692. doi: 10.1038/s41588-018-0086-z. Epub 2018 Apr 16.
• [5] Poor outcome of patients with pulmonary adenocarcinoma showing decreased E-cadherin combined with increased S100A4 expression.Int J Oncol. 2006 Jun;28(6):1369-74.
• [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] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [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] 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.
• [13] 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.
• [14] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.