Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3WSQE1)

• DOT Name: Glypican-2 (GPC2)
• Gene Name: GPC2
• Related Disease:
  Advanced cancer
  Breast cancer
  Liver cancer
  Malignant neoplasm
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
• UniProt ID: GPC2_HUMAN
• PDB ID: 6WJL; 7T62
• Pfam ID: PF01153
• Sequence:
  MSALRPLLLLLLPLCPGPGPGPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLR
  VCPQEYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQH
  SLTQLFSHSYGRLYAQHALIFNGLFSRLRDFYGESGEGLDDTLADFWAQLLERVFPLLHP
  QYSFPPDYLLCLSRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQGLETGRNVVSE
  ALKVPVSEGCSQALMRLIGCPLCRGVPSLMPCQGFCLNVVRGCLSSRGLEPDWGNYLDGL
  LILADKLQGPFSFELTAESIGVKISEGLMYLQENSAKVSAQVFQECGPPDPVPARNRRAP
  PPREEAGRLWSMVTEEERPTTAAGTNLHRLVWELRERLARMRGFWARLSLTVCGDSRMAA
  DASLEAAPCWTGAGRGRYLPPVVGGSPAEQVNNPELKVDASGPDVPTRRRRLQLRAATAR
  MKTAALGHDLDGQDADEDASGSGGGQQYADDWMAGAVAPPARPPRPPYPPRRDGSGGKGG
  GGSARYNQGRSRSGGASIGFHTQTILILSLSALALLGPR
• Function: Cell surface proteoglycan that bears heparan sulfate. May fulfill a function related to the motile behaviors of developing neurons.
• Reactome Pathway:
  HS-GAG biosynthesis (R-HSA-2022928)
  HS-GAG degradation (R-HSA-2024096)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective EXT2 causes exostoses 2 (R-HSA-3656237)
  Defective EXT1 causes exostoses 1, TRPS2 and CHDS (R-HSA-3656253)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Attachment and Entry (R-HSA-9694614)
  Retinoid metabolism and transport (R-HSA-975634)
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)

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	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	Altered Expression	[2]
Malignant neoplasm	DISS6SNG	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[5]

10 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 Glypican-2 (GPC2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glypican-2 (GPC2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Glypican-2 (GPC2).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Glypican-2 (GPC2).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Glypican-2 (GPC2).	[10]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Glypican-2 (GPC2).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glypican-2 (GPC2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glypican-2 (GPC2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glypican-2 (GPC2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Glypican-2 (GPC2).	[15]

References

• [1] Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells.Cancer Res. 2001 Jul 15;61(14):5562-9.
• [2] Glypicans as Cancer Therapeutic Targets.Trends Cancer. 2018 Nov;4(11):741-754. doi: 10.1016/j.trecan.2018.09.004. Epub 2018 Sep 28.
• [3] Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.Cancer Cell. 2017 Sep 11;32(3):295-309.e12. doi: 10.1016/j.ccell.2017.08.003.
• [4] Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma.Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):E6623-E6631. doi: 10.1073/pnas.1706055114. Epub 2017 Jul 24.
• [5] Scratching the Surface of Immunotherapeutic Targets in Neuroblastoma.Cancer Cell. 2017 Sep 11;32(3):271-273. doi: 10.1016/j.ccell.2017.08.011.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] 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.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.