Details of Drug Off-Target (DOT)

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

• DOT Name: Nucleoside diphosphate kinase 6 (NME6)
• Synonyms: NDK 6; NDP kinase 6; EC 2.7.4.6; Inhibitor of p53-induced apoptosis-alpha; IPIA-alpha; nm23-H6
• Gene Name: NME6
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Crohn disease
• UniProt ID: NDK6_HUMAN
• EC Number: 2.7.4.6
• Pfam ID: PF00334
• Sequence:
  MASILRSPQALQLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFY
  REHEGRFFYQRLVEFMASGPIRAYILAHKDAIQLWRTLMGPTRVFRARHVAPDSIRGSFG
  LTDTRNTTHGSDSVVSASREIAAFFPDFSEQRWYEEEEPQLRCGPVCYSPEGGVHYVAGT
  GGLGPA
• Function: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Inhibitor of p53-induced apoptosis.
• Tissue Specificity: Expressed at a moderately low level in many tissues. Most abundant in kidney, prostate, ovary, intestine, and spleen.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Nucleoside diphosphate kinase 6 (NME6).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleoside diphosphate kinase 6 (NME6).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleoside diphosphate kinase 6 (NME6).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleoside diphosphate kinase 6 (NME6).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nucleoside diphosphate kinase 6 (NME6).	[8]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Nucleoside diphosphate kinase 6 (NME6).	[9]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Nucleoside diphosphate kinase 6 (NME6).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleoside diphosphate kinase 6 (NME6).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleoside diphosphate kinase 6 (NME6).	[13]

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 decreases the methylation of Nucleoside diphosphate kinase 6 (NME6).	[12]

References

• [1] Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer.J Pathol. 2005 Apr;205(5):623-32. doi: 10.1002/path.1724.
• [2] Identification of a Potential Regulatory Variant for Colorectal Cancer Risk Mapping to 3p21.31 in Chinese Population.Sci Rep. 2016 Apr 28;6:25194. doi: 10.1038/srep25194.
• [3] Gene expression and thiopurine metabolite profiling in inflammatory bowel disease - novel clues to drug targets and disease mechanisms?.PLoS One. 2013;8(2):e56989. doi: 10.1371/journal.pone.0056989. Epub 2013 Feb 21.
• [4] 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.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [10] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.