Drugbank Logo

Showing drug card for Trifluridine (DB00432)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:42
Primary Accession Number DB00432
Secondary Accession Number
  • APRD01275
Name Trifluridine
Drug Type
  • Approved
  • Small Molecule
Description An antiviral derivative of thymidine used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557)
Synonyms Not Available
Brand Names
  1. F3DThd
  2. F3T
  3. F3TDR
  4. Fluridine
  5. TFDU
  6. TFT
  7. Trifluoromethyldeoxyuridine
  8. Trifluorothymidine
  9. Trifluridina [INN-Spanish]
  10. Trifluridine [USAN:INN]
  11. Trifluridinum [INN-Latin]
  12. Virophta
  13. Viroptic
  14. trifluorothymine deoxyriboside
Brand Mixtures Not Available
Chemical IUPAC Name 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione
Chemical Formula C10H11F3N2O5
Chemical Structure Structure
CAS Registry Number 70-00-8
InChI Identifier InChI=1/C10H11F3N2O5/c11-10(12,13)4-2-15(9(19)14-8(4)18)7-1-5(17)6(3-16)20-7/h2,5-7,16-17H,1,3H2,(H,14,18,19)/t5-,6+,7+/m0/s1/f/h14H
InChI Key VSQQQLOSPVPRAZ-FKWPSYMCDZ
KEGG Drug D00391 Link Image
KEGG Compound Not Available
PubChem Compound 6256 Link Image
PubChem Substance 7847457 Link Image
ChEBI ID Not Available
PharmGKB ID PA451775 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02248529 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/trifluridine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Trifluridine Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 296.1999
Monoisotopic Molecular Weight 296.0620
State Solid
Melting Point 186-189 oC
Experimental Water Solubility 1560 mg/L Source: PhysProp
Predicted Water Solubility 6.69e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.7 Source: PhysProp
Predicted LogP -0.45 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.65 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 7.95
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(C(=O)NC1=O)C(F)(F)F
Canonical SMILES OCC1OC(CC1O)N1C=C(C(=O)NC1=O)C(F)(F)F
Drug Category
  • Antimetabolites
  • Antiviral Agents
ATC Codes
AHFS Codes
  • 52:04.20
Indication Ophthalmic solution for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.
Pharmacology Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vacciniavirus. Some strains of adenovirus are also inhibited in vitro. Trifluridine is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, trifluridine was also effective. Trifluridine interferes with DNA synthesis in cultured mammalian cells. However, its antiviral mechanism of action is not completely known.
Mechanism of Action Trifluridine interferes with DNA synthesis in cultured mammalian cells. Trifluridine presumably stops replication of herpes viral DNA in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. Trifluridine targets HSV and VSV thymidine kinase.
Absorption Systemic absorption of trifluridine following therapeutic dosing with trifluridine ophthalmic appears to be negligible.
Toxicity Overdosage by ocular instillation is unlikely because any excess solution should be quickly expelled from the conjunctival sac. Acute overdosage by accidental oral ingestion has not occurred. However, should such ingestion occur, the 75 mg dosage of trifluridine in a 7.5 mL bottle of trifluridine is not likely to produce adverse effects. Single intravenous doses of 1.5 to 30 mg/kg/day in children and adults with neoplastic disease produce reversible bone marrow depression as the only potentially serious toxic effect and only after three to five courses of therapy. The acute oral LD50 in the mouse and rat was 4379 mg/kg or higher.
Protein Binding Not Available
Biotransformation One major metabolite, 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea, indicating localized metabolism.
Half Life Approximately 12 to 18 minutes following ophthalmic administration.
Dosage Forms
Form Route
Solution Ophthalmic
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Costin D, Dogaru M, Popa AS, Cijevschi I: [Trifluridine therapy in herpetic in keratitis] Rev Med Chir Soc Med Nat Iasi. 2004 Apr-Jun;108(2):409-12. [PubMed Link Image]
  2. O'Brien WJ, Taylor JL: Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents. Invest Ophthalmol Vis Sci. 1991 Aug;32(9):2455-61. [PubMed Link Image]
  3. Kuster P, Taravella M, Gelinas M, Stepp P: Delivery of trifluridine to human cornea and aqueous using collagen shields. CLAO J. 1998 Apr;24(2):122-4. [PubMed Link Image]
  4. Wikipedia Link Image
  5. RxList Link Image
Organisms Affected
  • Human Herpes Virus
Targets
  1. DNA polymerase
  2. Thymidylate synthase
  3. Thymidine kinase
Drug Target 1 [top]
Target 1 ID 338
Target 1 Name DNA polymerase
Target 1 Synonyms
  1. EC 2.7.7.7
Target 1 Gene Name UL30
Target 1 Protein Sequence >DNA polymerase 
MFSGGGGPLSPGGKSAARAASGFFAPAGPRGASRGPPPCLRQNFYNPYLAPVGTQQKPTG
PTQRHTYYSECDEFRFIAPRVLDEDAPPEKRAGVHDGHLKRAPKVYCGGDERDVLRVGSG
GFWPRRSRLWGGVDHAPAGFNPTVTVFHVYDILENVEHAYGMRAAQFHARFMDAITPTGT
VITLLGLTPEGHRVAVHVYGTRQYFYMNKEEVDRHLQCRAPRDLCERMAAALRESPGASF
RGISADHFEAEVVERTDVYYYETRPALFYRVYVRSGRVLSYLCDNFCPAIKKYEGGVDAT
TRFILDNPGFVTFGWYRLKPGRNNTLAQPAAPMAFGTSSDVEFNCTADNLAIEGGMSDLP
AYKLMCFDIECKAGGEDELAFPVAGHPEDLVIQISCLLYDLSTTALEHVLLFSLGSCDLP
ESHLNELAARGLPTPVVLEFDSEFEMLLAFMTLVKQYGPEFVTGYNIINFDWPFLLAKLT
DIYKVPLDGYGRMNGRGVFRVWDIGQSHFQKRSKIKVNGMVNIDMYGIITDKIKLSSYKL
NAVAEAVLKDKKKDLSYRDIPAYYAAGPAQRGVIGEYCIQDSLLVGQLFFKFLPHLELSA
VARLAGINITRTIYDGQQIRVFTCLLRLADQKGFILPDTQGRFRGAGGEAPKRPAAARED
EERPEEEGEDEDEREEGGGEREPEGARETAGRHVGYQGARVLDPTSGFHVNPVVVFDFAS
LYPSIIQAHNLCFSTLSLRADAVAHLEAGKDYLEIEVGGRRLFFVKAHVRESLLSILLRD
WLAMRKQIRSRIPQSSPEEAVLLDKQQAAIKVVCNSVYGFTGVQHGLLPCLHVAATVTTI
GREMLLATREYVHARWAAFEQLLADFPEAADMRAPGPYSMRIIYGDTDSIFVLCRGLTAA
GLTAVGDKMASHISRALFLPPIKLECEKTFTKLLLIAKKKYIGVIYGGKMLIKGVDLVRK
NNCAFINRTSRALVDLLFYDDTVSGAAAALAERPAEEWLARPLPEGLQAFGAVLVDAHRR
ITDPERDIQDFVLTAELSRHPRAYTNKRLAHLTVYYKLMARRAQVPSIKDRIPYVIVAQT
REVEETVARLAALRELDAAAPGDEPAPPAALPSPAKRPRETPSPADPPGGASKPRKLLVS
ELAEDPAYAIAHGVALNTDYYFSHLLGAACVTFKALFGNNAKITESLLKRFIPEVWHPPD
DVAARLRTAGFGAVGAGATAEETRRMLHRAFDTLA
Target 1 Number of Residues 1255
Target 1 Molecular Weight 136422
Target 1 Theoretical pI 7.31
Target 1 GO Classification
Function
hydrolase activity
hydrolase activity, acting on ester bonds
nuclease activity
exonuclease activity
3'-5' exonuclease activity
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
DNA-directed DNA polymerase activity
nucleic acid binding
DNA binding
binding
nucleotide binding
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA replication
Component
Not Available
Target 1 General Function Replication, recombination and repair
Target 1 Specific Function Not Available
Target 1 Pathways
Name SMPDB Link KEGG Link
DNA polymerase map03030 Link Image
Purine metabolism SMP00050 Link Image map00230 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 1 Reactions
  • deoxynucleoside triphosphate + DNAn = diphosphate + DNAn+1
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 59530 Link Image
Target 1 UniProtKB/Swiss-Prot ID P04293 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name DPOL_HHV11 Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Nucleus
Target 1 Gene Sequence >3708 bp 
ATGTTTTCCGGTGGCGGCGGCCCGCTGTCCCCCGGAGGAAAGTCGGCGGCCAGGGCGGCG
TCCGGGTTTTTTGCGCCCGCCGGCCCTCGCGGAGCCAGCCGGGGACCCCCGCCTTGTTTG
AGGCAAAACTTTTACAACCCCTACCTCGCCCCAGTCGGGACGCAACAGAAGCCGACCGGG
CCAACCCAGCGCCATACGTACTATAGCGAATGCGATGAATTTCGATTCATCGCCCCGCGG
GTGCTGGACGAGGATGCCCCCCCGGAGAAGCGCGCCGGGGTGCACGACGGTCACCTCAAG
CGCGCCCCCAAGGTGTACTGCGGGGGGGACGAGCGCGACGTCCTCCGCGTCGGGTCGGGC
GGCTTCTGGCCGCGGCGCTCGCGCCTGTGGGGCGGCGTGGACCACGCCCCGGCGGGGTTC
AACCCCACCGTCACCGTCTTTCACGTGTACGACATCCTGGAGAACGTGGAGCACGCGTAC
GGCATGCGCGCGGCCCAGTTCCACGCGCGGTTTATGGACGCCATCACACCGACGGGGACC
GTCATCACGCTCCTGGGCCTGACTCCGGAAGGCCACCGGGTGGCCGTTCACGTTTACGGC
ACGCGGCAGTACTTTTACATGAACAAGGAGGAGGTCGACAGGCACCTACAATGCCGCGCC
CCACGAGATCTCTGCGAGCGCATGGCCGCGGCCCTGCGCGAGTCCCCGGGCGCGTCGTTC
CGCGGCATCTCCGCGGACCACTTCGAGGCGGAGGTGGTGGAGCGCACCGACGTGTACTAC
TACGAGACGCGCCCCGCTCTGTTTTACCGCGTCTACGTCCGAAGCGGGCGTGTGCTGTCG
TACCTGTGCGACAACTTCTGCCCGGCCATCAAGAAGTACGAGGGTGGGGTCGACGCCACC
ACCCGGTTCATCCTGGACAACCCCGGGTTCGTCACCTTCGGCTGGTACCGTCTCAAACCG
GGCCGGAACAACACGCTAGCCCAGCCGGCGGCCCCGATGGCCTTCGGGACATCCAGCGAC
GTCGAGTTTAACTGTACGGCGGACAACCTGGCCATCGAGGGGGGCATGAGCGACCTACCG
GCATACAAGCTCATGTGCTTCGATATCGAATGCAAGGCGGGGGGGGAGGACGAGCTGGCC
TTTCCGGTGGCCGGGCACCCGGAGGACCTGGTCATCCAGATATCCTGTCTGCTCTACGAC
CTGTCCACCACCGCCCTGGAGCACGTCCTCCTGTTTTCGCTCGGTTCCTGCGACCTCCCC
GAATCCCACCTGAACGAGCTGGCGGCCAGGGGCCTGCCCACGCCCGTGGTTCTGGAATTC
GACAGCGAATTCGAGATGCTGTTGGCCTTCATGACCCTTGTGAAACAGTACGGCCCCGAG
TTCGTGACCGGGTACAACATCATCAACTTCGACTGGCCCTTCTTGCTGGCCAAGCTGACG
GACATTTACAAGGTCCCCCTGGACGGGTACGGCCGCATGAACGGCCGGGGCGTGTTTCGC
GTGTGGGACATAGGCCAGAGCCACTTCCAGAAGCGCAGCAAGATAAAGGTGAACGGCATG
GTGAACATCGACATGTACGGGATTATAACCGACAAGATCAAGCTCTCGAGCTACAAGCTC
AACGCCGTGGCCGAAGCCGTCCTGAAGGACAAGAAGAAGGACCTGAGCTATCGCGACATC
CCCGCCTACTACGCCGCCGGGCCCGCGCAACGCGGGGTGATCGGCGAGTACTGCATACAG
GATTCCCTGCTGGTGGGCCAGCTGTTTTTTAAGTTTTTGCCCCATCTGGAGCTCTCGGCC
GTCGCGCGCTTGGCGGGTATTAACATCACCCGCACCATCTACGACGGCCAGCAGATCCGC
GTCTTTACGTGCCTGCTGCGCCTGGCCGACCAGAAGGGCTTTATTCTGCCGGACACCCAG
GGGCGATTTAGGGGCGCCGGGGGGGAGGCGCCCAAGCGTCCGGCCGCAGCCCGGGAGGAC
GAGGAGCGGCCAGAGGAGGAGGGGGAGGACGAGGACGAACGCGAGGAGGGCGGGGGCGAG
CGGGAGCCGGAGGGCGCGCGGGAGACCGCCGGCAGGCACGTGGGGTACCAGGGGGCCAGG
GTCCTTGACCCCACTTCCGGGTTTCACGTGAACCCCGTGGTGGTGTTCGACTTTGCCAGC
CTGTACCCCAGCATCATCCAGGCCCACAACCTGTGCTTCAGCACGCTCTCCCTGAGGGCC
GACGCAGTGGCGCACCTGGAGGCGGGCAAGGACTACCTGGAGATCGAGGTGGGGGGGCGA
CGGCTGTTCTTCGTCAAGGCTCACGTGCGAGAGAGCCTCCTCAGCATCCTCCTGCGGGAC
TGGCTCGCCATGCGAAAGCAGATCCGCTCGCGGATTCCCCAGAGCAGCCCCGAGGAGGCC
GTGCTCCTGGACAAGCAGCAGGCCGCCATCAAGGTCGTGTGTAACTCGGTGTACGGGTTC
ACGGGAGTGCAGCACGGACTCCTGCCGTGCCTGCACGTTGCCGCGACGGTGACGACCATC
GGCCGCGAGATGCTGCTCGCGACCCGCGAGTACGTCCACGCGCGCTGGGCGGCCTTCGAA
CAGCTCCTGGCCGATTTCCCGGAGGCGGCCGACATGCGCGCCCCCGGGCCCTATTCCATG
CGCATCATCTACGGGGACACGGACTCCATCTTTGTGCTGTGCCGCGGCCTCACGGCCGCC
GGGCTGACGGCCGTGGGCGACAAGATGGCGAGCCACATCTCGCGCGCGCTGTTTCTGCCC
CCCATCAAACTCGAGTGCGAAAAGACGTTCACCAAGCTGCTGCTGATCGCCAAGAAAAAG
TACATCGGCGTCATCTACGGGGGTAAGATGCTCATCAAGGGCGTGGATCTGGTGCGCAAA
AACAACTGCGCGTTTATCAACCGCACCTCCAGGGCCCTGGTCGACCTGCTGTTTTACGAC
GATACCGTCTCCGGAGCGGCCGCCGCGTTAGCCGAGCGCCCCGCGGAGGAGTGGCTGGCG
CGACCCCTGCCCGAGGGACTGCAGGCGTTCGGGGCCGTCCTCGTAGACGCCCATCGGCGC
ATCACCGACCCGGAGAGGGACATCCAGGACTTTGTCCTCACCGCCGAACTGAGCAGACAC
CCGCGCGCGTACACCAACAAGCGCCTGGCCCACCTGACGGTGTATTACAAGCTCATGGCC
CGCCGCGCGCAGGTCCCGTCCATCAAGGACCGGATCCCGTACGTGATCGTGGCCCAGACC
CGCGAGGTAGAGGAGACGGTCGCGCGGCTGGCCGCCCTCCGCGAGCTAGACGCCGCCGCC
CCAGGGGACGAGCCCGCCCCCCCCGCGGCCCTGCCCTCCCCGGCCAAGCGCCCCCGGGAG
ACGCCGTCGCCTGCCGACCCCCCGGGAGGCGCGTCCAAGCCCCGCAAGCTGCTGGTGTCC
GAGCTGGCCGAGGATCCCGCATACGCCATTGCCCACGGCGTCGCCCTGAACACGGACTAT
TACTTCTCCCACCTGTTGGGGGCGGCGTGCGTGACATTCAAGGCCCTGTTTGGGAATAAC
GCCAAGATCACCGAGAGTCTGTTAAAAAGGTTTATTCCCGAAGTGTGGCACCCCCCGGAC
GACGTGGCCGCGCGGCTCCGGACCGCAGGGTTCGGGGCGGTGGGTGCCGGCGCTACGGCG
GAGGAAACTCGTCGAATGTTGCATAGAGCCTTTGATACTCTAGCATGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. McGeoch DJ, Dalrymple MA, Davison AJ, Dolan A, Frame MC, McNab D, Perry LJ, Scott JE, Taylor P: The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74. [PubMed Link Image]
  2. Quinn JP, McGeoch DJ: DNA sequence of the region in the genome of herpes simplex virus type 1 containing the genes for DNA polymerase and the major DNA binding protein. Nucleic Acids Res. 1985 Nov 25;13(22):8143-63. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 359
Target 2 Name Thymidylate synthase
Target 2 Synonyms
  1. EC 2.1.1.45
  2. TS
  3. TSase
Target 2 Gene Name TYMS
Target 2 Protein Sequence >Thymidylate synthase 
PVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFGM
QARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDSL
GFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMCA
WNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHIT
GLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEGY
NPHPTIKMEMAV
Target 2 Number of Residues 317
Target 2 Molecular Weight 35585
Target 2 Theoretical pI 7.00
Target 2 GO Classification
Function
catalytic activity
transferase activity
transferase activity, transferring one-carbon groups
methyltransferase activity
5,10-methylenetetrahydrofolate-dependent methyltransferase activity
thymidylate synthase activity
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleotide metabolism
pyrimidine nucleotide metabolism
pyrimidine nucleotide biosynthesis
pyrimidine nucleoside monophosphate biosynthesis
pyrimidine deoxyribonucleoside monophosphate biosynthesis
dTMP biosynthesis
Component
Not Available
Target 2 General Function Nucleotide transport and metabolism
Target 2 Specific Function Not Available
Target 2 Pathways
Name SMPDB Link KEGG Link
One carbon pool by folate SMP00053 Link Image map00670 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 2 Reactions
  • 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 37479 Link Image
Target 2 UniProtKB/Swiss-Prot ID P04818 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name TYSY_HUMAN Link Image
Target 2 PDB ID 1JUJ Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location Not Available
Target 2 Gene Sequence >942 bp 
ATGCCTGTGGCCGGCTCGGAGCTGCCGCGCCGGCCCTTGCCCCCCGCCGCACAGGAGCGG
GACGCCGAGCCGCGTCCGCCGCACGGGGAGCTGCAGTACCTGGGGCAGATCCAACACATC
CTCCGCTGCGGCGTCAGGAAGGACGACCGCACGGGCACCGGCACCCTGTCGGTATTCGGC
ATGCAGGCGCGCTACAGCCTGAGAGATGAATTCCCTCTGCTGACAACCAAACGTGTGTTC
TGGAAGGGTGTTTTGGAGGAGTTGCTGTGGTTTATCAAGGGATCCACAAATGCTAAAGAG
CTGTCTTCCAAGGGAGTGAAAATCTGGGATGCCAATGGATCCCGAGACTTTTTGGACAGC
CTGGGATTCTCCACCAGAGAAGAAGGGGACTTGGGCCCAGTTTATGGCTTCCAGTGGAGG
CATTTTGGGGCAGAATACAGAGATATGGAATCAGATTATTCAGGACAGGGAGTTGACCAA
CTGCAAAGAGTGATTGACACCATCAAAACCAACCCTGACGACAGAAGAATCATCATGTGC
GCTTGGAATCCAAGAGATCTTCCTCTGATGGCGCTGCCTCCATGCCATGCCCTCTGCCAG
TTCTATGTGGTGAACAGTGAGCTGTCCTGCCAGCTGTACCAGAGATCGGGAGACATGGGC
CTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCACGTACATGATTGCGCACATC
ACGGGCCTGAAGCCAGGTGACTTTATACACACTTTGGGAGATGCACATATTTACCTGAAT
CACATCGAGCCACTGAAAATTCAGCTTCAGCGAGAACCCAGACCTTTCCCAAAGCTCAGG
ATTCTTCGAAAAGTTGAGAAAATTGATGACTTCAAAGCTGAAGACTTTCAGATTGAAGGG
TACAATCCGCATCCAACTATTAAAATGGAAATGGCTGTTTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID TYMS Link Image
Target 2 GenAtlas ID TYMS Link Image
Target 2 HGNC ID HGNC:12441 Link Image
Target 2 Chromosome Location 18
Target 2 Locus 18p11.32
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Phan J, Steadman DJ, Koli S, Ding WC, Minor W, Dunlap RB, Berger SH, Lebioda L: Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors. J Biol Chem. 2001 Apr 27;276(17):14170-7. Epub 2001 Jan 24. [PubMed Link Image]
  2. Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L: Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry. 2001 Feb 20;40(7):1897-902. [PubMed Link Image]
  3. Kaneda S, Nalbantoglu J, Takeishi K, Shimizu K, Gotoh O, Seno T, Ayusawa D: Structural and functional analysis of the human thymidylate synthase gene. J Biol Chem. 1990 Nov 25;265(33):20277-84. [PubMed Link Image]
  4. Takeishi K, Kaneda S, Ayusawa D, Shimizu K, Gotoh O, Seno T: Human thymidylate synthase gene: isolation of phage clones which cover a functionally active gene and structural analysis of the region upstream from the translation initiation codon. J Biochem (Tokyo). 1989 Oct;106(4):575-83. [PubMed Link Image]
  5. Davisson VJ, Sirawaraporn W, Santi DV: Expression of human thymidylate synthase in Escherichia coli. J Biol Chem. 1989 Jun 5;264(16):9145-8. [PubMed Link Image]
  6. Takeishi K, Kaneda S, Ayusawa D, Shimizu K, Gotoh O, Seno T: Nucleotide sequence of a functional cDNA for human thymidylate synthase. Nucleic Acids Res. 1985 Mar 25;13(6):2035-43. [PubMed Link Image]
  7. Shimizu K, Ayusawa D, Takeishi K, Seno T: Purification and NH2-terminal amino acid sequence of human thymidylate synthase in an overproducing transformant of mouse FM3A cells. J Biochem (Tokyo). 1985 Mar;97(3):845-50. [PubMed Link Image]
  8. Schiffer CA, Clifton IJ, Davisson VJ, Santi DV, Stroud RM: Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry. 1995 Dec 19;34(50):16279-87. [PubMed Link Image]
Target 2 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 509
Target 3 Name Thymidine kinase
Target 3 Synonyms
  1. EC 2.7.1.21
Target 3 Gene Name TK
Target 3 Protein Sequence >Thymidine kinase 
MASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQEATEVRLEQKMPTLLRVYIDGPHGM
GKTTTTQLLVALGSRDDIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDAAVV
MTSAQITMGMPYAVTDAVLAPHIGGEAGSSHAPPPALTLIFDRHPIAALLCYPAARYLMG
SMTPQAVLAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRVYG
LLANTVRYLQGGGSWREDWGQLSGTAVPPQGAEPQSNAGPRPHIGDTLFTLFRAPELLAP
NGDLYNVFAWALDVLAKRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPGSIPT
ICDLARTFAREMGEAN
Target 3 Number of Residues 382
Target 3 Molecular Weight 40897
Target 3 Theoretical pI 7.70
Target 3 GO Classification
Function
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleobase, nucleoside, nucleotide kinase activity
nucleoside kinase activity
deoxynucleoside kinase activity
thymidine kinase activity
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleotide metabolism
pyrimidine nucleotide metabolism
pyrimidine nucleotide biosynthesis
pyrimidine nucleoside monophosphate biosynthesis
pyrimidine ribonucleoside monophosphate biosynthesis
TMP biosynthesis
Component
Not Available
Target 3 General Function Involved in thymidine kinase activity
Target 3 Specific Function In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome
Target 3 Pathways
Name SMPDB Link KEGG Link
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 3 Reactions
  • ATP + thymidine = ADP + thymidine 5'-phosphate
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 8100965 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q9QNF7 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name KITH_HHV1 Link Image
Target 3 PDB ID 1OF1 Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >1131 bp 
ATGGCTTCGTACCCCTGCCATCAACACGCGTCTGCGTTCGACCAGGCTGCGCGTTCTCGC
GGCCATAGCAACCGACGTACGGCGTTGCGCCCTCGCCGGCAGCAAGAAGCCACGGAAGTC
CGCCTGGAGCAGAAAATGCCCACGCTACTGCGGGTTTATATAGACGGTCCTCACGGGATG
GGGAAAACCACCACCACGCAACTGCTGGTGGCCCTGGGTTCGCGCGACGATATCGTCTAC
GTACCCGAGCCGATGACTTACTGGCAGGTGCTGGGGGCTTCCGAGACAATCGCGAACATC
TACACCACACAACACCGCCTCGACCAGGGTGAGATATCGGCCGGGGACGCGGCGGTGGTA
ATGACAAGCGCCCAGATAACAATGGGCATGCCTTATGCCGTGACCGACGCCGTTCTGGCT
CCTCATATCGGGGGGGAGGCTGGGAGCTCACATGCCCCGCCCCCGGCCCTCACCCTCATC
TTCGACCGCCATCCCATCGCCGCCCTCCTGTGCTACCCGGCCGCGCGATACCTTATGGGC
AGCATGACCCCCCAGGCCGTGCTGGCGTTCGTGGCCCTCATCCCGCCGACCTTGCCCGGC
ACAAACATCGTGTTGGGGGCCCTTCCGGAGGACAGACACATCGACCGCCTGGCCAAACGC
CAGCGCCCCGGCGAGCGGCTTGACCTGGCTATGCTGGCCGCGATTCGCCGCGTTTACGGG
CTGCTTGCCAATACGGTGCGGTATCTGCAGGGCGGCGGGTCGTGGCGGGAGGATTGGGGA
CAGCTTTCGGGGACGGCCGTGCCGCCCCAGGGTGCCGAGCCCCAGAGCAACGCGGGCCCA
CGACCCCATATCGGGGACACGTTATTTACCCTGTTTCGGGCCCCCGAGTTGCTGGCCCCC
AACGGCGACCTGTATAACGTGTTTGCCTGGGCCTTGGACGTCTTGGCCAAACGCCTCCGT
CCCATGCACGTCTTTATCCTGGATTACGACCAATCGCCCGCCGGCTGCCGGGACGCCCTG
CTGCAACTTACCTCCGGGATGGTCCAGACCCACGTCACCACCCCAGGCTCCATACCGACG
ATCTGCGACCTGGCGCGCACGTTTGCCCGGGAGATGGGGGAGGCTAACTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID Not Available
Target 3 GenAtlas ID Not Available
Target 3 HGNC ID Not Available
Target 3 Chromosome Location MT
Target 3 Locus -
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Nagamine M, Suzutani T, Saijo M, Hayashi K, Azuma M: Comparison of polymorphism of thymidine kinase gene and restriction fragment length polymorphism of genomic DNA in herpes simplex virus type 1. J Clin Microbiol. 2000 Jul;38(7):2750-2. [PubMed Link Image]
  2. Morfin F, Souillet G, Bilger K, Ooka T, Aymard M, Thouvenot D: Genetic characterization of thymidine kinase from acyclovir-resistant and -susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients. J Infect Dis. 2000 Jul;182(1):290-3. Epub 2000 Jun 19. [PubMed Link Image]
Target 3 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.