Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDWU4AC)

• DOT Name: UPF0524 protein C3orf70 (C3ORF70)
• Gene Name: C3ORF70
• UniProt ID: CC070_HUMAN
• Pfam ID: PF15823
• Sequence:
  MSAAASPASERGWKSEKLDEAQALARSCAARRPDFQPCDGLSICATHSHGKCFKLHWCCH
  LGWCHCKYMYQPMTPVEQLPSTEIPARPREPTNTIQISVSLTEHFLKFASVFQPPLPPDS
  PRYCMISDLFIDNYQVKCINGKMCYVQKQPAPHSHRMSPEEVSAHDALISKESNTPKIDH
  CSSPSSSEDSGINAIGAHYVESCDEDTEEGAELSSEEDYSPESSWEPDECTLLSPSQSDL
  EVIETIETTV
• Function: May play a role in neuronal and neurobehavioral development.

Molecular Interaction Atlas (MIA) of This DOT

9 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 UPF0524 protein C3orf70 (C3ORF70).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of UPF0524 protein C3orf70 (C3ORF70).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of UPF0524 protein C3orf70 (C3ORF70).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UPF0524 protein C3orf70 (C3ORF70).	[4]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of UPF0524 protein C3orf70 (C3ORF70).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of UPF0524 protein C3orf70 (C3ORF70).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of UPF0524 protein C3orf70 (C3ORF70).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of UPF0524 protein C3orf70 (C3ORF70).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of UPF0524 protein C3orf70 (C3ORF70).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of UPF0524 protein C3orf70 (C3ORF70).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of UPF0524 protein C3orf70 (C3ORF70).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of UPF0524 protein C3orf70 (C3ORF70).	[11]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] 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.