Details of Drug Off-Target (DOT)

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

• DOT Name: Arrestin domain-containing protein 2 (ARRDC2)
• Gene Name: ARRDC2
• UniProt ID: ARRD2_HUMAN
• Pfam ID: PF02752 ; PF00339
• Sequence:
  MLFDKVKAFSVQLDGATAGVEPVFSGGQAVAGRVLLELSSAARVGALRLRARGRAHVHWT
  ESRSAGSSTAYTQSYSERVEVVSHRATLLAPDTGETTTLPPGRHEFLFSFQLPPTLVTSF
  EGKHGSVRYCIKATLHRPWVPARRARKVFTVIEPVDINTPALLAPQAGAREKVARSWYCN
  RGLVSLSAKIDRKGYTPGEVIPVFAEIDNGSTRPVLPRAAVVQTQTFMARGARKQKRAVV
  ASLAGEPVGPGQRALWQGRALRIPPVGPSILHCRVLHVDYALKVCVDIPGTSKLLLELPL
  VIGTIPLHPFGSRSSSVGSHASFLLDWRLGALPERPEAPPEYSEVVADTEEAALGQSPFP
  LPQDPDMSLEGPFFAYIQEFRYRPPPLYSEEDPNPLLGDMRPRCMTC

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
Temozolomide	DMKECZD	Approved	Arrestin domain-containing protein 2 (ARRDC2) affects the response to substance of Temozolomide.	[12]
DTI-015	DMXZRW0	Approved	Arrestin domain-containing protein 2 (ARRDC2) affects the response to substance of DTI-015.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Arrestin domain-containing protein 2 (ARRDC2).	[1]

12 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 Arrestin domain-containing protein 2 (ARRDC2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Arrestin domain-containing protein 2 (ARRDC2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Arrestin domain-containing protein 2 (ARRDC2).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Arrestin domain-containing protein 2 (ARRDC2).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Arrestin domain-containing protein 2 (ARRDC2).	[11]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] 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.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.