Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEEHY1D)

• DOT Name: Syndecan-2 (SDC2)
• Synonyms: SYND2; Fibroglycan; Heparan sulfate proteoglycan core protein; HSPG; CD antigen CD362
• Gene Name: SDC2
• UniProt ID: SDC2_HUMAN
• PDB ID: 6ITH
• Pfam ID: PF01034
• Sequence:
  MRRAWILLTLGLVACVSAESRAELTSDKDMYLDNSSIEEASGVYPIDDDDYASASGSGAD
  EDVESPELTTSRPLPKILLTSAAPKVETTTLNIQNKIPAQTKSPEETDKEKVHLSDSERK
  MDPAEEDTNVYTEKHSDSLFKRTEVLAAVIAGGVIGFLFAIFLILLLVYRMRKKDEGSYD
  LGERKPSSAAYQKAPTKEFYA
• Function: Cell surface proteoglycan which regulates dendritic arbor morphogenesis.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Cytoskeleton in muscle cells (hsa04820)
  Malaria (hsa05144)
  Proteoglycans in cancer (hsa05205)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  HS-GAG biosynthesis (R-HSA-2022928)
  HS-GAG degradation (R-HSA-2024096)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Syndecan interactions (R-HSA-3000170)
  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)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  EPHB-mediated forward signaling (R-HSA-3928662)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Post-translational protein phosphorylation (R-HSA-8957275)
  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

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Syndecan-2 (SDC2) affects the response to substance of Cisplatin.	[24]
Mitoxantrone	DMM39BF	Approved	Syndecan-2 (SDC2) affects the response to substance of Mitoxantrone.	[24]

25 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 Syndecan-2 (SDC2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Syndecan-2 (SDC2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Syndecan-2 (SDC2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Syndecan-2 (SDC2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Syndecan-2 (SDC2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Syndecan-2 (SDC2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Syndecan-2 (SDC2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Syndecan-2 (SDC2).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Syndecan-2 (SDC2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Syndecan-2 (SDC2).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Syndecan-2 (SDC2).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Syndecan-2 (SDC2).	[12]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Syndecan-2 (SDC2).	[13]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Syndecan-2 (SDC2).	[14]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Syndecan-2 (SDC2).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Syndecan-2 (SDC2).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Syndecan-2 (SDC2).	[17]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Syndecan-2 (SDC2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Syndecan-2 (SDC2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Syndecan-2 (SDC2).	[19]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Syndecan-2 (SDC2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Syndecan-2 (SDC2).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Syndecan-2 (SDC2).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Syndecan-2 (SDC2).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Syndecan-2 (SDC2).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Syndecan-2 (SDC2).	[7]

References

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• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.
• [7] Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
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• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Gene expression profile changes in NB4 cells induced by arsenic trioxide. Acta Pharmacol Sin. 2003 Jul;24(7):646-50.
• [11] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009 Aug 21;138(4):645-659. doi: 10.1016/j.cell.2009.06.034. Epub 2009 Aug 13.
• [14] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [15] Biochemical and toxicological evaluation of nano-heparins in cell functional properties, proteasome activation and expression of key matrix molecules. Toxicol Lett. 2016 Jan 5;240(1):32-42. doi: 10.1016/j.toxlet.2015.10.005. Epub 2015 Oct 22.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [19] 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.
• [20] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [21] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.