Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVKVR34)

• DOT Name: Small VCP/p97-interacting protein (SVIP)
• Gene Name: SVIP
• Related Disease:
  Alpha-1 antitrypsin deficiency
  Glioma
  Neoplasm
• UniProt ID: SVIP_HUMAN
• Pfam ID: PF15811
• Sequence:
  MGLCFPCPGESAPPTPDLEEKRAKLAEAAERRQKEAASRGILDVQSVQEKRKKKEKIEKQ
  IATSGPPPEGGLRWTVS
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alpha-1 antitrypsin deficiency	DISQKEHW	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]

7 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 Small VCP/p97-interacting protein (SVIP).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small VCP/p97-interacting protein (SVIP).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Small VCP/p97-interacting protein (SVIP).	[5]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Small VCP/p97-interacting protein (SVIP).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Small VCP/p97-interacting protein (SVIP).	[7]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Small VCP/p97-interacting protein (SVIP).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Small VCP/p97-interacting protein (SVIP).	[10]

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 increases the methylation of Small VCP/p97-interacting protein (SVIP).	[8]

References

• [1] SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78.PLoS One. 2017 Mar 16;12(3):e0172983. doi: 10.1371/journal.pone.0172983. eCollection 2017.
• [2] Regulation of p53wt glioma cell proliferation by androgen receptor-mediated inhibition of small VCP/p97-interacting protein expression.Oncotarget. 2017 Apr 4;8(14):23142-23154. doi: 10.18632/oncotarget.15509.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] 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.
• [9] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [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.