Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYN9GX0)

• DOT Name: NAD kinase (NADK)
• Synonyms: EC 2.7.1.23; Poly(P)/ATP NAD kinase
• Gene Name: NADK
• Related Disease: Matthew-Wood syndrome
• UniProt ID: NADK_HUMAN
• PDB ID: 3PFN
• EC Number: 2.7.1.23
• Pfam ID: PF01513 ; PF20143
• Sequence:
  MEMEQEKMTMNKELSPDAAAYCCSACHGDETWSYNHPIRGRAKSRSLSASPALGSTKEFR
  RTRSLHGPCPVTTFGPKACVLQNPQTIMHIQDPASQRLTWNKSPKSVLVIKKMRDASLLQ
  PFKELCTHLMEENMIVYVEKKVLEDPAIASDESFGAVKKKFCTFREDYDDISNQIDFIIC
  LGGDGTLLYASSLFQGSVPPVMAFHLGSLGFLTPFSFENFQSQVTQVIEGNAAVVLRSRL
  KVRVVKELRGKKTAVHNGLGENGSQAAGLDMDVGKQAMQYQVLNEVVIDRGPSSYLSNVD
  VYLDGHLITTVQGDGVIVSTPTGSTAYAAAAGASMIHPNVPAIMITPICPHSLSFRPIVV
  PAGVELKIMLSPEARNTAWVSFDGRKRQEIRHGDSISITTSCYPLPSICVRDPVSDWFES
  LAQCLHWNVRKKQAHFEEEEEEEEEG
• Tissue Specificity: Widely expressed but not detected in skeletal muscle.
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Nicotinate metabolism (R-HSA-196807)
• BioCyc Pathway: MetaCyc:HS00233-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[1]

7 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 NAD kinase (NADK).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NAD kinase (NADK).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of NAD kinase (NADK).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of NAD kinase (NADK).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of NAD kinase (NADK).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of NAD kinase (NADK).	[13]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Nicotinamide-Adenine-Dinucleotide increases the phosphorylation of NAD kinase (NADK).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of NAD kinase (NADK).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NAD kinase (NADK).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NAD kinase (NADK).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of NAD kinase (NADK).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of NAD kinase (NADK).	[9]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of NAD kinase (NADK).	[10]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of NAD kinase (NADK).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of NAD kinase (NADK).	[11]

References

• [1] Functional annotation of rare gene aberration drivers of pancreatic cancer.Nat Commun. 2016 Jan 25;7:10500. doi: 10.1038/ncomms10500.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] 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.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] A second target of benzamide riboside: dihydrofolate reductase. Cancer Biol Ther. 2012 Nov;13(13):1290-8.