Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCS3NYZ)

• DOT Name: Nucleoside diphosphate-linked moiety X motif 6 (NUDT6)
• Synonyms: Nudix motif 6; EC 3.6.1.-; Antisense basic fibroblast growth factor; Protein GFG
• Gene Name: NUDT6
• Related Disease:
  Adult hepatocellular carcinoma
  Bladder cancer
  Bronchiolitis obliterans syndrome
  Craniosynostosis
  Depression
  Endometriosis
  Hepatocellular carcinoma
  Liver cancer
  Medulloblastoma
  Non-insulin dependent diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Esophageal adenocarcinoma
  Small-cell lung cancer
  Colorectal carcinoma
• UniProt ID: NUDT6_HUMAN
• PDB ID: 3FXT; 3H95
• EC Number: 3.6.1.-
• Pfam ID: PF00293 ; PF18290
• Sequence:
  MRQPLSWGRWRAMLARTYGPGPSAGYRWASGAQGYVRNPPVGACDLQGELDRFGGISVRL
  ARLDALDRLDAAAFQKGLQAAVQQWRSEGRTAVWLHIPILQSRFIAPAASLGFCFHHAES
  DSSTLTLWLREGPSRLPGYASHQVGVAGAVFDESTRKILVVQDRNKLKNMWKFPGGLSEP
  EEDIGDTAVREVFEETGIKSEFRSVLSIRQQHTNPGAFGKSDMYIICRLKPYSFTINFCQ
  EECLRCEWMDLNDLAKTENTTPITSRVARLLLYGYREGFDKIDLTVEELPAVYTGLFYKL
  YHKELPENYKTMKGID
• Function: May contribute to the regulation of cell proliferation.
• Tissue Specificity: Detected in liver, kidney and esophagus (at protein level). Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult hepatocellular carcinoma	DIS6ZPAI	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Bronchiolitis obliterans syndrome	DISCK9IV	Strong	Altered Expression	[3]
Craniosynostosis	DIS6J405	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Biomarker	[5]
Endometriosis	DISX1AG8	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[8]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[9]
Esophageal adenocarcinoma	DISODWFP	moderate	Biomarker	[9]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[11]

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 Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[24]

2 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 Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleoside diphosphate-linked moiety X motif 6 (NUDT6).	[21]

References

• [1] Precision Oncology for Hepatocellular Cancer: Slivering the Liver by FGF19-FGF4-KLB Pathway Inhibition.Cancer Discov. 2019 Dec;9(12):1646-1649. doi: 10.1158/2159-8290.CD-19-1156.
• [2] Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor.Clin Cancer Res. 2000 Nov;6(11):4422-31.
• [3] Obliterative airway remodelling in transplanted and non-transplanted lungs.Virchows Arch. 2010 Sep;457(3):369-80. doi: 10.1007/s00428-010-0949-x. Epub 2010 Jul 15.
• [4] Craniosynostosis, psychomotor retardation, and facial dysmorphic features in a Spanish patient with a 4q27q28.3 deletion.Childs Nerv Syst. 2014 Dec;30(12):2157-61. doi: 10.1007/s00381-014-2474-8. Epub 2014 Jul 1.
• [5] Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice.Front Mol Neurosci. 2018 Oct 12;11:377. doi: 10.3389/fnmol.2018.00377. eCollection 2018.
• [6] Different basic fibroblast growth factor and fibroblast growth factor-antisense expression in eutopic endometrial stromal cells derived from women with and without endometriosis.J Clin Endocrinol Metab. 2003 Jun;88(6):2853-9. doi: 10.1210/jc.2002-021434.
• [7] Antitumor activity of fibroblast growth factors (FGFs) for medulloblastoma may correlate with FGF receptor expression and tumor variant.Clin Cancer Res. 2002 Jan;8(1):246-57.
• [8] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [9] Alternative splicing of the FGF antisense gene: differential subcellular localization in human tissues and esophageal adenocarcinoma.J Mol Med (Berl). 2007 Nov;85(11):1215-28. doi: 10.1007/s00109-007-0219-9. Epub 2007 Jun 14.
• [10] Inhibition of fibroblast growth factor 2-induced apoptosis involves survivin expression, protein kinase C alpha activation and subcellular translocation of Smac in human small cell lung cancer cells.Acta Biochim Biophys Sin (Shanghai). 2008 Apr;40(4):297-303. doi: 10.1111/j.1745-7270.2008.00401.x.
• [11] A potential proliferative gene, NUDT6, is down-regulated by green tea catechins at the posttranscriptional level.J Nutr Biochem. 2010 Feb;21(2):98-106. doi: 10.1016/j.jnutbio.2008.11.002. Epub 2009 Jan 20.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] 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.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 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.
• [17] 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.
• [18] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [19] 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.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] 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.
• [22] 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.
• [23] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [24] 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.