Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS3NCC5)

• DOT Name: Syntenin-1 (SDCBP)
• Synonyms: Melanoma differentiation-associated protein 9; MDA-9; Pro-TGF-alpha cytoplasmic domain-interacting protein 18; TACIP18; Scaffold protein Pbp1; Syndecan-binding protein 1
• Gene Name: SDCBP
• Related Disease:
  Glioma
  Advanced cancer
  Brain cancer
  Brain neoplasm
  Colon cancer
  Colon carcinoma
  Estrogen-receptor positive breast cancer
  Head-neck squamous cell carcinoma
  Lung adenocarcinoma
  Melanoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Uveal Melanoma
  Autoimmune disease
  Metastatic malignant neoplasm
  Metastatic melanoma
  Triple negative breast cancer
  Adult glioblastoma
  Breast cancer
  Breast carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Human papillomavirus infection
  Lung cancer
  Lung carcinoma
  Neuroendocrine neoplasm
  Osteoarthritis
• UniProt ID: SDCB1_HUMAN
• PDB ID: 1N99 ; 1NTE ; 1OBX ; 1OBY ; 1OBZ ; 1R6J ; 1V1T ; 1W9E ; 1W9O ; 1W9Q ; 1YBO ; 4Z33 ; 6R9H ; 6RLC ; 7FSG ; 7FSH ; 7FSI ; 7FSJ ; 7FSK ; 7FSL ; 7FSM ; 7FSN ; 7FSO ; 7FSP ; 7FSQ ; 7FSR ; 7FSS ; 7FST ; 7FSU ; 7FSV ; 7FSW ; 7FSX ; 7FSY ; 7FSZ ; 7FT0 ; 7FT1 ; 7FT2 ; 7FT3 ; 7FT4 ; 7FT5 ; 7FT6 ; 7FT7 ; 7FT8 ; 7FT9 ; 7FTA ; 7FTB ; 7FTC ; 7FTD ; 8AAI ; 8AAK ; 8AAO ; 8AAP ; 8BLU ; 8BLV ; 8HCK
• Pfam ID: PF00595
• Sequence:
  MSLYPSLEDLKVDKVIQAQTAFSANPANPAILSEASAPIPHDGNLYPRLYPELSQYMGLS
  LNEEEIRANVAVVSGAPLQGQLVARPSSINYMVAPVTGNDVGIRRAEIKQGIREVILCKD
  QDGKIGLRLKSIDNGIFVQLVQANSPASLVGLRFGDQVLQINGENCAGWSSDKAHKVLKQ
  AFGEKITMTIRDRPFERTITMHKDSTGHVGFIFKNGKITSIVKDSSAARNGLLTEHNICE
  INGQNVIGLKDSQIADILSTSGTVVTITIMPAFIFEHIIKRMAPSIMKSLMDHTIPEV
• Function: Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis. Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1. In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis. Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types. In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA). May also play a role in vesicular trafficking. Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway.
• Tissue Specificity: Expressed in lung cancers, including adenocarcinoma, squamous cell carcinoma and small-cell carcinoma (at protein level) . Widely expressed. Expressed in fetal kidney, liver, lung and brain. In adult highest expression in heart and placenta.
• Reactome Pathway:
  Neurofascin interactions (R-HSA-447043)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  Regulation of necroptotic cell death (R-HSA-5675482)
  Neutrophil degranulation (R-HSA-6798695)
  Ephrin signaling (R-HSA-3928664)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Brain cancer	DISBKFB7	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[5]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[7]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Uveal Melanoma	DISA7ZGL	Strong	Altered Expression	[10]
Autoimmune disease	DISORMTM	moderate	Biomarker	[11]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[12]
Metastatic melanoma	DISSL43L	moderate	Biomarker	[13]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[14]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[15]
Breast cancer	DIS7DPX1	Limited	Biomarker	[16]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[16]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[8]
Human papillomavirus infection	DISX61LX	Limited	Biomarker	[17]
Lung cancer	DISCM4YA	Limited	Altered Expression	[18]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[18]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[18]
Osteoarthritis	DIS05URM	Limited	Biomarker	[19]

24 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 Syntenin-1 (SDCBP).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Syntenin-1 (SDCBP).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Syntenin-1 (SDCBP).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Syntenin-1 (SDCBP).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Syntenin-1 (SDCBP).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntenin-1 (SDCBP).	[25]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Syntenin-1 (SDCBP).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Syntenin-1 (SDCBP).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Syntenin-1 (SDCBP).	[22]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Syntenin-1 (SDCBP).	[28]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Syntenin-1 (SDCBP).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Syntenin-1 (SDCBP).	[30]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Syntenin-1 (SDCBP).	[31]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Syntenin-1 (SDCBP).	[32]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Syntenin-1 (SDCBP).	[31]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Syntenin-1 (SDCBP).	[33]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols decreases the expression of Syntenin-1 (SDCBP).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Syntenin-1 (SDCBP).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntenin-1 (SDCBP).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Syntenin-1 (SDCBP).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Syntenin-1 (SDCBP).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Syntenin-1 (SDCBP).	[30]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Syntenin-1 (SDCBP).	[41]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Syntenin-1 (SDCBP).	[42]

3 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 Syntenin-1 (SDCBP).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Syntenin-1 (SDCBP).	[38]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Syntenin-1 (SDCBP).	[38]

References

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