Details of Drug Off-Target (DOT)

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

• DOT Name: Catenin delta-1 (CTNND1)
• Synonyms: Cadherin-associated Src substrate; CAS; p120 catenin; p120(ctn); p120(cas)
• Gene Name: CTNND1
• Related Disease:
  Adult glioblastoma
  Blepharocheilodontic syndrome 2
  Colon carcinoma
  Glioblastoma multiforme
  Advanced cancer
  Alzheimer disease
  Atherosclerosis
  Carcinoma
  Childhood apraxia of speech
  Colon cancer
  Colorectal carcinoma
  Dermatitis
  Ductal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Hepatocellular carcinoma
  Leukemia
  Lung adenocarcinoma
  Melanocytic nevus
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Precancerous condition
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Tuberculosis
  Type-1/2 diabetes
  Adenocarcinoma
  Breast neoplasm
  Carotid stenosis
  Extrapulmonary tuberculosis
  Head-neck squamous cell carcinoma
  Metastatic malignant neoplasm
  Pancreatic cancer
  Blepharocheilodontic syndrome
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Bone osteosarcoma
  Dental caries
  Glioma
  Melanoma
  Obesity
  Osteosarcoma
• UniProt ID: CTND1_HUMAN
• PDB ID: 3L6X; 3L6Y
• Pfam ID: PF00514
• Sequence:
  MDDSEVESTASILASVKEQEAQFEKLTRALEEERRHVSAQLERVRVSPQDANPLMANGTL
  TRRHQNGRFVGDADLERQKFSDLKLNGPQDHSHLLYSTIPRMQEPGQIVETYTEEDPEGA
  MSVVSVETSDDGTTRRTETTVKKVVKTVTTRTVQPVAMGPDGLPVDASSVSNNYIQTLGR
  DFRKNGNGGPGPYVGQAGTATLPRNFHYPPDGYSRHYEDGYPGGSDNYGSLSRVTRIEER
  YRPSMEGYRAPSRQDVYGPQPQVRVGGSSVDLHRFHPEPYGLEDDQRSMGYDDLDYGMMS
  DYGTARRTGTPSDPRRRLRSYEDMIGEEVPSDQYYWAPLAQHERGSLASLDSLRKGGPPP
  PNWRQPELPEVIAMLGFRLDAVKSNAAAYLQHLCYRNDKVKTDVRKLKGIPVLVGLLDHP
  KKEVHLGACGALKNISFGRDQDNKIAIKNCDGVPALVRLLRKARDMDLTEVITGTLWNLS
  SHDSIKMEIVDHALHALTDEVIIPHSGWEREPNEDCKPRHIEWESVLTNTAGCLRNVSSE
  RSEARRKLRECDGLVDALIFIVQAEIGQKDSDSKLVENCVCLLRNLSYQVHREIPQAERY
  QEAAPNVANNTGPHAASCFGAKKGKDEWFSRGKKPIEDPANDTVDFPKRTSPARGYELLF
  QPEVVRIYISLLKESKTPAILEASAGAIQNLCAGRWTYGRYIRSALRQEKALSAIADLLT
  NEHERVVKAASGALRNLAVDARNKELIGKHAIPNLVKNLPGGQQNSSWNFSEDTVISILN
  TINEVIAENLEAAKKLRETQGIEKLVLINKSGNRSEKEVRAAALVLQTIWGYKELRKPLE
  KEGWKKSDFQVNLNNASRSQSSHSYDDSTLPLIDRNQKSDKKPDREEIQMSNMGSNTKSL
  DNNYSTPNERGDHNRTLDRSGDLGDMEPLKGTTPLMQDEGQESLEEELDVLVLDDEGGQV
  SYPSMQKI
• Function: Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability. Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics. Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors.
• Tissue Specificity: Expressed in vascular endothelium. Melanocytes and melanoma cells primarily express the long isoform 1A, whereas keratinocytes express shorter isoforms, especially 3A. The shortest isoform 4A, is detected in normal keratinocytes and melanocytes, and generally lost from cells derived from squamous cell carcinomas or melanomas. The C-terminal alternatively spliced exon B is present in the p120ctn transcripts in the colon, intestine and prostate, but lost in several tumor tissues derived from these organs.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Adherens junction (hsa04520)
  Leukocyte transendothelial migration (hsa04670)
• Reactome Pathway:
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  InlA-mediated entry of Listeria monocytogenes into host cells (R-HSA-8876493)
  Regulation of CDH11 function (R-HSA-9762292)
  Regulation of CDH19 Expression and Function (R-HSA-9764302)
  CDH11 homotypic and heterotypic interactions (R-HSA-9833576)
  Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Blepharocheilodontic syndrome 2	DISKFOGQ	Definitive	Autosomal dominant	[2]
Colon carcinoma	DISJYKUO	Definitive	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Childhood apraxia of speech	DISIR974	Strong	Genetic Variation	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Dermatitis	DISY5SZC	Strong	Biomarker	[10]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Leukemia	DISNAKFL	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[16]
Melanocytic nevus	DISYS32D	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[12]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[12]
Precancerous condition	DISV06FL	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[24]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[26]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[27]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[28]
Carotid stenosis	DISZA8D0	moderate	Biomarker	[29]
Extrapulmonary tuberculosis	DIS6KM28	moderate	Genetic Variation	[30]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[31]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[28]
Pancreatic cancer	DISJC981	moderate	Biomarker	[32]
Blepharocheilodontic syndrome	DIS3K312	Supportive	Autosomal dominant	[33]
Lung cancer	DISCM4YA	Disputed	Altered Expression	[16]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[16]
Lung neoplasm	DISVARNB	Disputed	Biomarker	[34]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[35]
Dental caries	DISRBCMD	Limited	Biomarker	[36]
Glioma	DIS5RPEH	Limited	Biomarker	[37]
Melanoma	DIS1RRCY	Limited	Posttranslational Modification	[38]
Obesity	DIS47Y1K	Limited	Genetic Variation	[39]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Catenin delta-1 (CTNND1) decreases the response to substance of Arsenic trioxide.	[61]

17 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 Catenin delta-1 (CTNND1).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Catenin delta-1 (CTNND1).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Catenin delta-1 (CTNND1).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Catenin delta-1 (CTNND1).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Catenin delta-1 (CTNND1).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Catenin delta-1 (CTNND1).	[46]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Catenin delta-1 (CTNND1).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Catenin delta-1 (CTNND1).	[50]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Catenin delta-1 (CTNND1).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Catenin delta-1 (CTNND1).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Catenin delta-1 (CTNND1).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Catenin delta-1 (CTNND1).	[54]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Catenin delta-1 (CTNND1).	[55]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Catenin delta-1 (CTNND1).	[56]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Catenin delta-1 (CTNND1).	[57]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Catenin delta-1 (CTNND1).	[58]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Catenin delta-1 (CTNND1).	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Catenin delta-1 (CTNND1).	[44]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Catenin delta-1 (CTNND1).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Catenin delta-1 (CTNND1).	[49]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Catenin delta-1 (CTNND1).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Catenin delta-1 (CTNND1).	[44]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Catenin delta-1 (CTNND1).	[60]

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