Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXX1OWL)

• DOT Name: Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14)
• Synonyms: UDPG pyrophosphatase; UGPPase; EC 3.6.1.45; Nucleoside diphosphate-linked moiety X motif 14; Nudix motif 14
• Gene Name: NUDT14
• UniProt ID: NUD14_HUMAN
• PDB ID: 3Q91
• EC Number: 3.6.1.45
• Sequence:
  MERIEGASVGRCAASPYLRPLTLHYRQNGAQKSWDFMKTHDSVTVLLFNSSRRSLVLVKQ
  FRPAVYAGEVERRFPGSLAAVDQDGPRELQPALPGSAGVTVELCAGLVDQPGLSLEEVAC
  KEAWEECGYHLAPSDLRRVATYWSGVGLTGSRQTMFYTEVTDAQRSGPGGGLVEEGELIE
  VVHLPLEGAQAFADDPDIPKTLGVIFGVSWFLSQVAPNLDLQ
• Function: Hydrolyzes UDP-glucose to glucose 1-phosphate and UMP and ADP-ribose to ribose 5-phosphate and AMP. The physiological substrate is probably UDP-glucose. Poor activity on other substrates such as ADP-glucose, CDP-glucose, GDP-glucose and GDP-mannose.
• Reactome Pathway: Synthesis of dolichyl-phosphate-glucose (R-HSA-480985)

Molecular Interaction Atlas (MIA) of This DOT

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 Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Uridine diphosphate glucose pyrophosphatase NUDT14 (NUDT14).	[6]

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] 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.
• [3] 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.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] 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.
• [6] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.