Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMYE5LJ)

• Drug Name: DEOXYCYTIDINE Drug Info
• Synonyms: Cytosine deoxyribonucleoside; 2'-dC; bmse000323; ACMC-209rv6; CYTIDINE, 2'-DEOXY-; Cytosine deoxy nucleoside hydrochloride; 4-amino-1-[4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one; Desoxycytidine; 4-amino-1-(2-deoxypentofuranosyl)pyrimidin-2(1H)-one; 4-amino-1-[4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2-one; 3h-deoxycytidine; 4-amino-1-(4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one; 40093-94-5; AC1L19OG; TimTec1_003892; NCIOpen2_004589; Oprea1_817993

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[1]

• Cross-matching ID:
  PubChem CID: 13711
  ChEBI ID: CHEBI:15698
  CAS Number: CAS 951-77-9
  TTD Drug ID: DMYE5LJ

Molecule-Related Drug Atlas

Drug(s) Targeting Thymidine kinase 1 (TK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Penciclovir	DMOUMDV	Herpes simplex labialis	1F00.01	Approved	[5]
TK-DLI	DM26I8H	Graft-versus-host disease	4B24	Preregistration	[6]
FV-100	DMZARP1	Varicella zoster virus infection	1E91	Phase 3	[7]
Radiosensitizer gene therapy	DMN1ZEU	Pancreatic cancer	2C10	Phase 3	[8]
RP101	DMNIYSZ	Infectious disease	1A00-CA43.1	Phase 2/3	[9]
HQK-1004	DM3WX0K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
Rilapladib	DMB9861	Arteriosclerosis	BD40	Phase 1	[11]
Ad-OC-hsvTK/valacyclovir	DM9GLHO	Prostate cancer	2C82.0	Phase 1	[12]
Thymidine kinase-expressing adenovirus and ganciclovir suicide gene therapy	DMO8SGD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
Sitimagene ceradenovec	DM0T2QV	Brain cancer	2A00	Discontinued in Phase 3	[14]

Drug(s) Affected By Deoxycytidine kinase (DCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[16]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[17]
Emtricitabine	DMBMUWZ	Hepatitis virus infection	1E50-1E51	Approved	[3]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[19]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[20]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[21]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[23]

Drug(s) Affected By Sodium/nucleoside cotransporter 1 (SLC28A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Uridine	DMQTREB	Depression	6A70-6A7Z	Approved	[4]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[25]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[27]
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[27]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[28]
Azacitidine	DMTA5OE	Acute myelogenous leukaemia	2A41	Approved	[28]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Thymidine kinase 1 (TK1)	TTP3QRF	KITH_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Deoxycytidine kinase (DCK)	OTW8HLZC	DCK_HUMAN	Protein Interaction/Cellular Processes	[3]
Sodium/nucleoside cotransporter 1 (SLC28A1)	OTXWVV9O	S28A1_HUMAN	Regulation of Drug Effects	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Species- or isozyme-specific enzyme inhibitors. 5. Differential effects of thymidine substituents on affinity for rat thymidine kinase isozymes. J Med Chem. 1982 Jun;25(6):644-9.
• [3] Nonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-nucleosides. J Med Chem. 2007 Jun 28;50(13):3004-14. doi: 10.1021/jm0700215. Epub 2007 May 27.
• [4] Differential transport of cytosine-containing nucleosides by recombinant human concentrative nucleoside transporter protein hCNT1. Nucleosides Nucleotides Nucleic Acids. 2000 Jan-Feb;19(1-2):415-34. doi: 10.1080/15257770008033018.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Company report (Takara Bio)
• [7] Specific recognition of the bicyclic pyrimidine nucleoside analogs, a new class of highly potent and selective inhibitors of varicella-zoster virus (VZV), by the VZV-encoded thymidine kinase. Mol Pharmacol. 2002 Feb;61(2):249-54.
• [8] Pronounced antitumor effects and tumor radiosensitization of double suicide gene therapy. Clin Cancer Res. 1997 Nov;3(11):2081-8.
• [9] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [10] Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr Opin Oncol. 2001 Sep;13(5):360-7.
• [11] Trichomonas vaginalis thymidine kinase: purification, characterization and search for inhibitors. Biochem J. 1998 Aug 15;334 ( Pt 1):15-22.
• [12] Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum Gene Ther. 2003 Feb 10;14(3):227-41.
• [13] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [14] Sitimagene ceradenovec: a gene-based drug for the treatment of operable high-grade glioma. Future Oncol. 2010 Nov;6(11):1691-710.
• [15] 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.
• [16] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [17] 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.
• [18] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [19] 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.
• [20] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [22] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [23] 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.
• [24] 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.
• [25] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [26] 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.
• [27] Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol. 1997 Feb;272(2 Pt 1):C707-14. doi: 10.1152/ajpcell.1997.272.2.C707.
• [28] Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation. Mol Cancer Ther. 2009 Jan;8(1):225-31. doi: 10.1158/1535-7163.MCT-08-0743.
• [29] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.