Details of Drug Off-Target (DOT)

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

• DOT Name: Vinexin (SORBS3)
• Synonyms: SH3-containing adapter molecule 1; SCAM-1; Sorbin and SH3 domain-containing protein 3
• Gene Name: SORBS3
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Coronary atherosclerosis
  Coronary heart disease
  Alzheimer disease
  Hepatocellular carcinoma
  Neoplasm
  Obesity
• UniProt ID: VINEX_HUMAN
• PDB ID: 2CT3; 2DLM; 2NWM; 2YUP
• Pfam ID: PF00018 ; PF14604 ; PF02208
• Sequence:
  MQGPPRSLRAGLSLDDFIPGHLQSHIGSSSRGTRVPVIRNGGSNTLNFQFHDPAPRTVCN
  GGYTPRRDASQHPDPAWYQTWPGPGSKPSASTKIPASQHTQNWSATWTKDSKRRDKRWVK
  YEGIGPVDESGMPIAPRSSVDRPRDWYRRMFQQIHRKMPDLQLDWTFEEPPRDPRHLGAQ
  QRPAHRPGPATSSSGRSWDHSEELPRSTFNYRPGAFSTVLQPSNQVLRRREKVDNVWTEE
  SWNQFLQELETGQRPKKPLVDDPGEKPSQPIEVLLERELAELSAELDKDLRAIETRLPSP
  KSSPAPRRAPEQRPPAGPASAWSSSYPHAPYLGSARSLSPHKMADGGSPFLGRRDFVYPS
  STRDPSASNGGGSPARREEKKRKAARLKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEG
  EHHGRLGIFPANYVEVLPADEIPKPIKPPTYQVLEYGEAVAQYTFKGDLEVELSFRKGEH
  ICLIRKVNENWYEGRITGTGRQGIFPASYVQVSREPRLRLCDDGPQLPTSPRLTAAARSA
  RHPSSPSALRSPADPIDLGGQTSPRRTGFSFPTQEPRPQTQNLGTPGPALSHSRGPSHPL
  DLGTSSPNTSQIHWTPYRAMYQYRPQNEDELELREGDRVDVMQQCDDGWFVGVSRRTQKF
  GTFPGNYVAPV
• Function: Vinexin alpha isoform promotes up-regulation of actin stress fiber formation. Vinexin beta isoform plays a role in cell spreading and enhances the activation of JNK/SAPK in response to EGF stimulation by using its third SH3 domain.
• Tissue Specificity: Both isoforms are expressed in different tissues like heart, placenta, brain, skeletal muscle and pancreas. Isoform beta is especially found in liver.
• Reactome Pathway: Smooth Muscle Contraction (R-HSA-445355)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Biomarker	[1]
Atherosclerosis	DISMN9J3	Definitive	Biomarker	[1]
Coronary atherosclerosis	DISKNDYU	Definitive	Altered Expression	[1]
Coronary heart disease	DIS5OIP1	Definitive	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Vinexin (SORBS3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Vinexin (SORBS3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Vinexin (SORBS3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Vinexin (SORBS3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vinexin (SORBS3).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Vinexin (SORBS3).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Vinexin (SORBS3).	[11]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Vinexin (SORBS3).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Vinexin (SORBS3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Vinexin (SORBS3).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Vinexin (SORBS3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Vinexin (SORBS3).	[17]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Vinexin (SORBS3).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Vinexin (SORBS3).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Vinexin (SORBS3).	[16]

References

• [1] Vinexin Ablation Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice by Inactivating the Akt-Nuclear Factor B Inflammatory Axis.J Am Heart Assoc. 2017 Feb 16;6(2):e004585. doi: 10.1161/JAHA.116.004585.
• [2] Alzheimer's Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters.Neuropsychobiology. 2019;78(2):79-85. doi: 10.1159/000497164. Epub 2019 May 16.
• [3] Chromosome 8p tumor suppressor genes SH2D4A and SORBS3 cooperate to inhibit interleukin-6 signaling in hepatocellular carcinoma.Hepatology. 2016 Sep;64(3):828-42. doi: 10.1002/hep.28684. Epub 2016 Jul 15.
• [4] Alterations of sorbin and SH3 domain containing 3 (SORBS3) in human skeletal muscle following Roux-en-Y gastric bypass surgery.Clin Epigenetics. 2017 Sep 2;9:96. doi: 10.1186/s13148-017-0396-5. eCollection 2017.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] 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.
• [12] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [18] 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.