Details of Drug Off-Target (DOT)

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

• DOT Name: Cadherin-22 (CDH22)
• Synonyms: Pituitary and brain cadherin; PB-cadherin
• Gene Name: CDH22
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Glioma
  Invasive ductal breast carcinoma
  Neoplasm
• UniProt ID: CAD22_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MRPRPEGRGLRAGVALSPALLLLLLLPPPPTLLGRLWAAGTPSPSAPGARQDGALGAGRV
  KRGWVWNQFFVVEEYTGTEPLYVGKIHSDSDEGDGAIKYTISGEGAGTIFLIDELTGDIH
  AMERLDREQKTFYTLRAQARDRATNRLLEPESEFIIKVQDINDSEPRFLHGPYIGSVAEL
  SPTGTSVMQVMASDADDPTYGSSARLVYSVLDGEHHFTVDPKTGVIRTAVPDLDRESQER
  YEVVIQATDMAGQLGGLSGSTTVTIVVTDVNDNPPRFPQKMYQFSIQESAPIGTAVGRVK
  AEDSDVGENTDMTYHLKDESSSGGDVFKVTTDSDTQEAIIVVQKRLDFESQPVHTVILEA
  LNKFVDPRFADLGTFRDQAIVRVAVTDVDEPPEFRPPSGLLEVQEDAQVGSLVGVVTARD
  PDAANRPVRYAIDRESDLDQIFDIDADTGAIVTGKGLDRETAGWHNITVLAMEADNHAQL
  SRASLRIRILDVNDNPPELATPYEAAVCEDAKPGQLIQTISVVDRDEPQGGHRFYFRLVP
  EAPSNPHFSLLDIQDNTAAVHTQHVGFNRQEQDVFFLPILVVDSGPPTLSSTGTLTIRIC
  GCDSSGTIQSCNTTAFVMAASLSPGALIALLVCVLILVVLVLLILTLRRHHKSHLSSDED
  EDMRDNVIKYNDEGGGEQDTEAYDMSALRSLYDFGELKGGDGGGSAGGGAGGGSGGGAGS
  PPQAHLPSERHSLPQGPPSPEPDFSVFRDFISRKVALADGDLSVPPYDAFQTYAFEGADS
  PAASLSSLHSGSSGSEQDFAYLSSWGPRFRPLAALYAGHRGDDEAQAS
• 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. PB-cadherins may have a role in the morphological organization of pituitary gland and brain tissues.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[4]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Cadherin-22 (CDH22).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cadherin-22 (CDH22).	[6]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Cadherin-22 (CDH22).	[7]

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 decreases the methylation of Cadherin-22 (CDH22).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cadherin-22 (CDH22).	[9]

References

• [1] Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment.Clin Cancer Res. 2015 Aug 15;21(16):3695-704. doi: 10.1158/1078-0432.CCR-14-2457. Epub 2015 May 5.
• [2] Electrochemical immunosensor for CDH22 biomarker based on benzaldehyde substituted poly(phosphazene) modified disposable ITO electrode: A new fabrication strategy for biosensors.Biosens Bioelectron. 2019 Feb 1;126:230-239. doi: 10.1016/j.bios.2018.10.051. Epub 2018 Nov 2.
• [3] CDH22 hypermethylation is an independent prognostic biomarker in breast cancer.Clin Epigenetics. 2017 Jan 24;9:7. doi: 10.1186/s13148-016-0309-z. eCollection 2017.
• [4] Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive cancer cell migration, invasion and adhesion.Oncogene. 2018 Feb 1;37(5):651-662. doi: 10.1038/onc.2017.372. Epub 2017 Oct 9.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [8] 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.
• [9] 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.