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

General Information of Drug (ID: DM9OEJT)

• Drug Name: 2'-deoxythymidine triphosphate Drug Info
• Synonyms: Thymidine-5'-triphosphate; dTTP; thymidine 5'-triphosphate; Deoxy-TTP; Deoxythymidine 5'-triphosphate; 2'-Deoxythymidine triphosphate; 5'-TTP; THYMIDINE-5'-TRIPHOSPHATE; thymidine 5'-(tetrahydrogen triphosphate); TTP (nucleotide); thymidine triphosphate; pppdT; TTP; UNII-QOP4K539MU; 5-Methyl-dUTP; dThd5'PPP; CHEBI:18077; EINECS 206-669-7; QOP4K539MU; CHEMBL363559; 2'-Deoxythymidine 5'-triphosphate; 18423-43-3; [hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy]phosphoryl] phosphono hydrogen phosphate; DEOXYTHYMIDINE_TRIPHOSPHATE; Thymidine-5'-Triphosphate

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 64968
  ChEBI ID: CHEBI:18077
  CAS Number: CAS 365-08-2
  TTD Drug ID: DM9OEJT

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Reverse transcriptase (HIV RT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[5]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[6]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[7]
Tenofovir	DM1IS6U	Chronic hepatitis B virus infection		Approved	[5]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[8]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[9]
Delavirdine	DM3NF5G	Human immunodeficiency virus infection	1C62	Approved	[8]
Efavirenz	DMC0GSJ	Human immunodeficiency virus infection	1C62	Approved	[8]
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[10]
Etravirine	DMGV8QU	Human immunodeficiency virus-1 infection	1C62	Approved	[11]

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	[4]
DEOXYCYTIDINE	DMYE5LJ	Acute myeloid leukaemia	2A60	Approved	[12]
TK-DLI	DM26I8H	Graft-versus-host disease	4B24	Preregistration	[13]
FV-100	DMZARP1	Varicella zoster virus infection	1E91	Phase 3	[14]
Radiosensitizer gene therapy	DMN1ZEU	Pancreatic cancer	2C10	Phase 3	[15]
RP101	DMNIYSZ	Infectious disease	1A00-CA43.1	Phase 2/3	[16]
HQK-1004	DM3WX0K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
Rilapladib	DMB9861	Arteriosclerosis	BD40	Phase 1	[18]
Ad-OC-hsvTK/valacyclovir	DM9GLHO	Prostate cancer	2C82.0	Phase 1	[19]
Thymidine kinase-expressing adenovirus and ganciclovir suicide gene therapy	DMO8SGD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]

Drug(s) Targeting Herpes simplex virus DNA polymerase UL30 (HSV UL30)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[8]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[22]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[23]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[8]
Valganciclovir	DMS2IUH	Virus infection	1A24-1D9Z	Approved	[24]
Penciclovir	DMOUMDV	Herpes simplex labialis	1F00.01	Approved	[25]
Famciclovir	DMJHLSD	Meniere disease	AB31.0	Approved	[26]
Valacyclovir Hydrochloride	DM5I1CE	Herpes simplex virus infection	1F00	Approved	[8]
Foscavir	DM9KJLZ	Cytomegalovirus retinitis	9B72.00	Approved	[24]

Drug(s) Targeting Mycobacterium Thymidine monophosphate kinase (MycB tmk)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[4]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[27]
Deoxythymidine	DMR90HY	Discovery agent	N.A.	Investigative	[4]
Diphosphate	DMHY30B	Discovery agent	N.A.	Investigative	[4]
Thymidine-5'-Phosphate	DMKM6NQ	Discovery agent	N.A.	Investigative	[4]
P1-(5'-Adenosyl)P5-(5'-Thymidyl)Pentaphosphate	DMM4VWD	Discovery agent	N.A.	Investigative	[16]
3'-Azido-3'-Deoxythymidine-5'-Monophosphate	DMU08MN	Discovery agent	N.A.	Investigative	[4]
5-Hydroxymethyluridine-2'-Deoxy-5'-Monophosphate	DMWVCJ1	Discovery agent	N.A.	Investigative	[4]
CHLORODEOXYURIDINE	DMQT3WJ	Discovery agent	N.A.	Investigative	[28]
BROMODEOXYURIDINE	DM0D7LA	Discovery agent	N.A.	Investigative	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Herpes simplex virus DNA polymerase UL30 (HSV UL30)	TTIU7X1	DPOL_HHV11	Inhibitor	[2]
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[3]
Mycobacterium Thymidine monophosphate kinase (MycB tmk)	TT5B8AX	KTHY_MYCTU	Inhibitor	[4]
Thymidine kinase 1 (TK1)	TTP3QRF	KITH_HUMAN	Inhibitor	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5505).
• [2] Inhibition of human hepatitis B virus DNA polymerase and duck hepatitis B virus DNA polymerase by triphosphates of thymidine analogs and pharmacokinetic properties of the corresponding nucleosides. JMed Virol. 1988 Dec;26(4):353-62.
• [3] Synthesis of 2',3'-dideoxynucleoside 5'-alpha-P-borano-beta,gamma-(difluoromethylene)triphosphates and their inhibition of HIV-1 reverse transcript... J Med Chem. 2005 Apr 7;48(7):2695-700.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
• [6] HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.Nat Struct Mol Biol.2012 Jan 22;19(2):253-9.
• [7] A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model. J Biomol Struct Dyn. 1998 Oct;16(2):347-54.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only Curr HIV Res. 2009 May;7(3):320-6.
• [10] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [11] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [12] 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.
• [13] Company report (Takara Bio)
• [14] 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.
• [15] Pronounced antitumor effects and tumor radiosensitization of double suicide gene therapy. Clin Cancer Res. 1997 Nov;3(11):2081-8.
• [16] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [17] 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.
• [18] Trichomonas vaginalis thymidine kinase: purification, characterization and search for inhibitors. Biochem J. 1998 Aug 15;334 ( Pt 1):15-22.
• [19] 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.
• [20] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [21] Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72.
• [22] Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009 Feb;30(2):77-81.
• [23] Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient. Oral Microbiol Immunol. 2009 Apr;24(2):109-15.
• [24] Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22.
• [25] Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66.
• [26] Penciclovir cream--improved topical treatment for herpes simplex infections. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8.
• [27] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [28] Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: synthesis and in vitro anti-mycobacterial ac... Bioorg Med Chem. 2008 Jun 1;16(11):6075-85.