Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXR6VDI)

• DOT Name: Adenosine kinase (ADK)
• Synonyms: AK; EC 2.7.1.20; Adenosine 5'-phosphotransferase
• Gene Name: ADK
• Related Disease: Adenosine kinase deficiency
• UniProt ID: ADK_HUMAN
• PDB ID: 1BX4; 2I6A; 2I6B; 4O1L
• EC Number: 2.7.1.20
• Pfam ID: PF00294
• Sequence:
  MAAAEEEPKPKKLKVEAPQALRENILFGMGNPLLDISAVVDKDFLDKYSLKPNDQILAED
  KHKELFDELVKKFKVEYHAGGSTQNSIKVAQWMIQQPHKAATFFGCIGIDKFGEILKRKA
  AEAHVDAHYYEQNEQPTGTCAACITGDNRSLIANLAAANCYKKEKHLDLEKNWMLVEKAR
  VCYIAGFFLTVSPESVLKVAHHASENNRIFTLNLSAPFISQFYKESLMKVMPYVDILFGN
  ETEAATFAREQGFETKDIKEIAKKTQALPKMNSKRQRIVIFTQGRDDTIMATESEVTAFA
  VLDQDQKEIIDTNGAGDAFVGGFLSQLVSDKPLTECIRAGHYAASIIIRRTGCTFPEKPD
  FH
• Function: Catalyzes the phosphorylation of the purine nucleoside adenosine at the 5' position in an ATP-dependent manner. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.
• Tissue Specificity: Widely expressed. Highest level in placenta, liver, muscle and kidney.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway:
  Ribavirin ADME (R-HSA-9755088)
  Purine salvage (R-HSA-74217)
• BioCyc Pathway: MetaCyc:HS08097-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
Adenosine kinase deficiency	DIS058X7	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Adenosine kinase (ADK).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenosine kinase (ADK).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Adenosine kinase (ADK).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Adenosine kinase (ADK).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adenosine kinase (ADK).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Adenosine kinase (ADK).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Adenosine kinase (ADK).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Adenosine kinase (ADK).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Adenosine kinase (ADK).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Adenosine kinase (ADK).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Adenosine kinase (ADK).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Adenosine kinase (ADK).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Adenosine kinase (ADK).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Adenosine kinase (ADK).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Adenosine kinase (ADK).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Adenosine kinase (ADK).	[19]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Adenosine kinase (ADK).	[20]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Adenosine kinase (ADK).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Adenosine kinase (ADK).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Adenosine kinase (ADK).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adenosine kinase (ADK).	[12]

References

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• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [5] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [6] 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.
• [7] 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.
• [8] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] 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.
• [13] Species-specific toxicity of diclofenac and troglitazone in primary human and rat hepatocytes. Chem Biol Interact. 2009 Apr 15;179(1):17-24.
• [14] 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.
• [15] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [21] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.