Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUYF0H3)

• DOT Name: ADP-ribose pyrophosphatase, mitochondrial (NUDT9)
• Synonyms: EC 3.6.1.13; ADP-ribose diphosphatase; ADP-ribose phosphohydrolase; Adenosine diphosphoribose pyrophosphatase; ADPR-PPase; Nucleoside diphosphate-linked moiety X motif 9; Nudix motif 9
• Gene Name: NUDT9
• Related Disease: Endometrial carcinoma
• UniProt ID: NUDT9_HUMAN
• PDB ID: 1Q33; 1QVJ
• EC Number: 3.6.1.13
• Pfam ID: PF00293
• Sequence:
  MAGRLLGKALAAVSLSLALASVTIRSSRCRGIQAFRNSFSSSWFHLNTNVMSGSNGSKEN
  SHNKARTSPYPGSKVERSQVPNEKVGWLVEWQDYKPVEYTAVSVLAGPRWADPQISESNF
  SPKFNEKDGHVERKSKNGLYEIENGRPRNPAGRTGLVGRGLLGRWGPNHAADPIITRWKR
  DSSGNKIMHPVSGKHILQFVAIKRKDCGEWAIPGGMVDPGEKISATLKREFGEEALNSLQ
  KTSAEKREIEEKLHKLFSQDHLVIYKGYVDDPRNTDNAWMETEAVNYHDETGEIMDNLML
  EAGDDAGKVKWVDINDKLKLYASHSQFIKLVAEKRDAHWSEDSEADCHAL
• Function: Hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate.
• Tissue Specificity: Ubiquitously expressed but isoform 1 is the most predominant isoform.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[1]

7 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 ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[5]
Magnesium	DMU4ORS	Approved	Magnesium increases the activity of ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[6]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[7]
Manganese	DMKT129	Investigative	Manganese increases the activity of ADP-ribose pyrophosphatase, mitochondrial (NUDT9).	[6]

References

• [1] Differential expression of NUDT9 at different phases of the menstrual cycle and in different components of normal and neoplastic human endometrium.Taiwan J Obstet Gynecol. 2009 Jun;48(2):96-107. doi: 10.1016/S1028-4559(09)60266-7.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] 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.
• [6] The specific, submicromolar-Km ADP-ribose pyrophosphatase purified from human placenta is enzymically indistinguishable from recombinant NUDT9 protein, including a selectivity for Mn2+ as activating cation and increase in Km for ADP-ribose, both elicited by H2O2. Biochim Biophys Acta. 2006 Oct;1760(10):1545-51. doi: 10.1016/j.bbagen.2006.06.003. Epub 2006 Jun 9.
• [7] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.