Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9HT0O1)

• DOT Name: Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8)
• Synonyms: EC 3.6.1.-; Nucleoside diphosphate-linked moiety X motif 8; Nudix motif 8
• Gene Name: NUDT8
• UniProt ID: NUDT8_HUMAN
• EC Number: 3.6.1.-
• Pfam ID: PF00293
• Sequence:
  MLPDCLSAEGELRCRRLLAGATARLRARPASAAVLVPLCSVRGVPALLYTLRSSRLTGRH
  KGDVSFPGGKCDPADQDVVHTALRETREELGLAVPEEHVWGLLRPVYDPQKATVVPVLAG
  VGPLDPQSLRPNSEEVDEVFALPLAHLLQTQNQGYTHFCRGGHFRYTLPVFLHGPHRVWG
  LTAVITEFALQLLAPGTYQPRLAGLTCSGAEGLARPKQPLASPCQASSTPGLNKGL
• Function: Acyl-CoA diphosphatase that mediates the hydrolysis of a wide range of CoA and CoA esters yielding 3',5'-ADP and the corresponding 4'-phosphopantetheine derivative as products. Hydrolyzes short- and medium-chain acyl-CoAs, exhibiting the highest activity toward free CoA, hexanoyl-CoA, and octanoyl-CoA and the lowest activity against acetyl-CoA. Exhibits decapping activity towards dpCoA-capped RNAs in vitro.
• Reactome Pathway: Vitamin B5 (pantothenate) metabolism (R-HSA-199220)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mitochondrial coenzyme A diphosphatase NUDT8 (NUDT8).	[6]

References

• [1] 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.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.