Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKNLQU7)

• DOT Name: Cadherin-3 (CDH3)
• Synonyms: Placental cadherin; P-cadherin
• Gene Name: CDH3
• Related Disease:
  EEM syndrome
  Congenital hypotrichosis with juvenile macular dystrophy
• UniProt ID: CADH3_HUMAN
• PDB ID: 4OY9; 4ZML; 4ZMN; 4ZMO; 4ZMP; 4ZMQ; 4ZMT; 4ZMV; 4ZMW; 4ZMX; 4ZMY; 4ZMZ; 5JYL; 5JYM; 6ZTB; 6ZTR; 7CME; 7CMF; 8HYI
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFMGCPG
  QEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPISVPENG
  KGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIAK
  YELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLPGTSVMQVTAT
  DEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDREKVPEYTLTIQA
  TDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSP
  AWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAKNQHTLYVEVTNEAPFVLKL
  PTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPVCVYTAEDPDKENQKISYRILR
  DPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYEVMVLAMDNGSPPTTGTGTLLLTLID
  VNDHGPVPEPRQITICNQSPVRQVLNITDKDLSPHTSPFQAQLTDDSDIYWTAEVNEEGD
  TVVLSLKKFLKQDTYDVHLSLSDHGNKEQLTVIRATVCDCHGHVETCPGPWKGGFILPVL
  GAVLALLFLLLVLLLLVRKKRKIKEPLLLPEDDTRDNVFYYGEEGGGEEDQDYDITQLHR
  GLEARPEVVLRNDVAPTIIPTPMYRPRPANPDEIGNFIIENLKAANTDPTAPPYDTLLVF
  DYEGSGSDAASLSSLTSSASDQDQDYDYLNEWGSRFKKLADMYGGGEDD
• 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: Expressed in some normal epithelial tissues and in some carcinoma cell lines.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
EEM syndrome	DISLQBDE	Definitive	Autosomal recessive	[1]
Congenital hypotrichosis with juvenile macular dystrophy	DISQD3X1	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cadherin-3 (CDH3) affects the response to substance of Cisplatin.	[25]

25 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-3 (CDH3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cadherin-3 (CDH3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cadherin-3 (CDH3).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Cadherin-3 (CDH3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cadherin-3 (CDH3).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cadherin-3 (CDH3).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cadherin-3 (CDH3).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Cadherin-3 (CDH3).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cadherin-3 (CDH3).	[12]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Cadherin-3 (CDH3).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cadherin-3 (CDH3).	[14]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Cadherin-3 (CDH3).	[15]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Cadherin-3 (CDH3).	[16]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Cadherin-3 (CDH3).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cadherin-3 (CDH3).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cadherin-3 (CDH3).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Cadherin-3 (CDH3).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cadherin-3 (CDH3).	[18]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Cadherin-3 (CDH3).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cadherin-3 (CDH3).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cadherin-3 (CDH3).	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Cadherin-3 (CDH3).	[22]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Cadherin-3 (CDH3).	[23]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Cadherin-3 (CDH3).	[24]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Cadherin-3 (CDH3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cadherin-3 (CDH3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cadherin-3 (CDH3).	[17]

References

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• [13] High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Br J Nutr. 2008 Apr;99(4):703-8.
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• [20] Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAF(V600E) mutation. J Cell Mol Med. 2021 Feb;25(3):1739-1749. doi: 10.1111/jcmm.16279. Epub 2021 Jan 19.
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• [23] 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.
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