Details of Drug Off-Target (DOT)

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

• DOT Name: Chondroitin sulfate proteoglycan 5 (CSPG5)
• Synonyms: Acidic leucine-rich EGF-like domain-containing brain protein; Neuroglycan C
• Gene Name: CSPG5
• Related Disease:
  Sotos syndrome
  Schizophrenia
  Dengue
• UniProt ID: CSPG5_HUMAN
• Pfam ID: PF06566 ; PF06567
• Sequence:
  MGRAGGGGPGRGPPPLLLFLGAALVLASGAVPAREAGSAVEAEELVKGSPAWEPPANDTR
  EEAGPPAAGEDEASWTAPGGELAGPEEVLQESAAVTGTAWLEADSPGLGGVTAEAGSGDA
  QALPATLQAPHEVLGQSIMPPAIPEATEASGPPSPTPGDKLSPASELPKESPLEVWLNLG
  GSTPDPQGPELTYPFQGTLEPQPASDIIDIDYFEGLDGEGRGADLGSFPGSPGTSENHPD
  TEGETPSWSLLDLYDDFTPFDESDFYPTTSFYDDLDEEEEEEEDDKDAVGGGDLEDENEL
  LVPTGKPGLGPGTGQPTSRWHAVPPQHTLGSVPGSSIALRPRPGEPGRDLASSENGTECR
  SGFVRHNGSCRSVCDLFPSYCHNGGQCYLVENIGAFCRCNTQDYIWHKGMRCESIITDFQ
  VMCVAVGSAALVLLLLFMMTVFFAKKLYLLKTENTKLRRTNKFRTPSELHNDNFSLSTIA
  EGSHPNVRKLCNTPRTSSPHARALAHYDNVICQDDPSAPHKIQEVLKSCLKEEESFNIQN
  SMSPKLEGGKGDQADLDVNCLQNNLT
• Function: May function as a growth and differentiation factor involved in neuritogenesis. May induce ERBB3 activation.
• Tissue Specificity: Detected in cerebrospinal fluid (at protein level) . Detected in urine (at protein level) . Expressed in brain (at protein level) .
• Reactome Pathway:
  Chondroitin sulfate biosynthesis (R-HSA-2022870)
  Dermatan sulfate biosynthesis (R-HSA-2022923)
  CS/DS degradation (R-HSA-2024101)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective CHST3 causes SEDCJD (R-HSA-3595172)
  Defective CHST14 causes EDS, musculocontractural type (R-HSA-3595174)
  Defective CHSY1 causes TPBS (R-HSA-3595177)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sotos syndrome	DISN4U1D	Definitive	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Dengue	DISKH221	Limited	Biomarker	[3]

12 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 Chondroitin sulfate proteoglycan 5 (CSPG5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[10]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[11]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Chondroitin sulfate proteoglycan 5 (CSPG5).	[16]

1 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 affects the methylation of Chondroitin sulfate proteoglycan 5 (CSPG5).	[13]

References

• [1] Cloning and chromosomal mapping of the human gene of neuroglycan C (NGC), a neural transmembrane chondroitin sulfate proteoglycan with an EGF module.Neurosci Res. 1998 Dec;32(4):313-22. doi: 10.1016/s0168-0102(98)00098-4.
• [2] The X-linked intellectual disability protein PHF6 associates with the PAF1 complex and regulates neuronal migration in the mammalian brain.Neuron. 2013 Jun 19;78(6):986-93. doi: 10.1016/j.neuron.2013.04.021.
• [3] Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations.Structure. 2019 Apr 2;27(4):618-630.e4. doi: 10.1016/j.str.2018.12.006. Epub 2019 Jan 24.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [9] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [10] 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.
• [11] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [12] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [16] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.