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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:43
Primary Accession Number DB00544
Secondary Accession Number
  • APRD00516
  • EXPT03204
Name Fluorouracil
Drug Type
  • Approved
  • Small Molecule
Description A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [PubChem]
Synonyms Not Available
Brand Names
  1. 5 Fluorouracil
  2. Adrucil
  3. Arumel
  4. Carac
  5. Carzonal
  6. Effluderm
  7. Efudex
  8. Efudix
  9. Efurix
  10. FU
  11. Fluoroblastin
  12. Fluoroplex
  13. Fluracil
  14. Fluracilum
  15. Fluri
  16. Fluril
  17. Fluro Uracil
  18. Ftoruracil
  19. Kecimeton
  20. Phthoruracil
  21. Phtoruracil
  22. Queroplex
  23. Timazin
  24. URF
  25. Ulup
Brand Mixtures Not Available
Chemical IUPAC Name 5-fluoro-1H-pyrimidine-2,4-dione
Chemical Formula C4H3FN2O2
Chemical Structure Structure
CAS Registry Number 51-21-8
InChI Identifier InChI=1/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)/f/h6-7H
InChI Key GHASVSINZRGABV-ZDKSUBDRCT
KEGG Drug D00584 Link Image
KEGG Compound C07649 Link Image
PubChem Compound 3385 Link Image
PubChem Substance 7847650 Link Image
ChEBI ID Not Available
PharmGKB ID PA449672 Link Image
HET ID URF Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02182742 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/carac.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Fluorouracil Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Heidelberger et al., U.S. Pat 2802005(1956)
Average Molecular Weight 130.0772
Monoisotopic Molecular Weight 130.0179
State Solid
Melting Point 280-282oC
Experimental Water Solubility < 0.1 g/100 mL at 19 °C Source: PhysProp
Predicted Water Solubility 5.86e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.8 Source: PhysProp
Predicted LogP -0.57 Calculated using ALOGPS
Experimental LogS -1.07 [ADME Research, USCD]
Predicted LogS -1.35 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.02
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 1H7X Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES FC1=CNC(=O)NC1=O
Canonical SMILES FC1=CNC(=O)NC1=O
Drug Category
  • Antimetabolites
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Immunosuppressive Agents
ATC Codes
AHFS Codes
  • 10:00.00
  • 84:92.00
Indication For the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, rectum, breast, stomach and pancrease.
Pharmacology Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.
Mechanism of Action Fluorouracil inhibits thymidylate synthetase, leading to inhibition of DNA and RNA synthesis and cell death.
Absorption 28-100%
Toxicity LD50=230mg/kg (orally in mice)
Protein Binding 8-12%
Biotransformation Hepatic
Half Life 10-20 minutes
Dosage Forms
Form Route
Cream Topical
Solution Intravenous
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The antineoplasic agent increases the anticoagulant effect
Anisindione The antineoplasic agent increases the anticoagulant effect
Cimetidine Cimetidine increases the effect and toxicity of fluorouracil
Dicumarol The antineoplasic agent increases the anticoagulant effect
Ethotoin Fluorouracil increases the effect of hydantoin
Fosphenytoin Fluorouracil increases the effect of hydantoin
Mephenytoin Fluorouracil increases the effect of hydantoin
Metronidazole Risk of 5-FU toxicity when associated with metronidazole
Phenytoin Fluorouracil increases the effect of hydantoin
Warfarin The antineoplasic agent increases the anticoagulant effect
Food Interactions
  • Vitamin B1 needs increased with long term use.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 1A2 (CYP1A2)
  2. Thymidine phosphorylase
Targets
  1. Thymidylate synthase
  2. Uridine phosphorylase
  3. Uracil phosphoribosyltransferase
  4. Dihydropyrimidine dehydrogenase [NADP+]
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 1 Gene Name CYP1A2
Enzyme 1 SwissProt ID P05177 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Thymidine phosphorylase
Enzyme 2 Gene Name ECGF1
Enzyme 2 SwissProt ID P19971 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P19971|TYPH_HUMAN Thymidine phosphorylase - Homo sapiens (Human). 
MAALMTPGTGAPPAPGDFSGEGSQGLPDPSPEPKQLPELIRMKRDGGRLSEADIRGFVAA
VVNGSAQGAQIGAMLMAIRLRGMDLEETSVLTQALAQSGQQLEWPEAWRQQLVDKHSTGG
VGDKVSLVLAPALAACGCKVPMISGRGLGHTGGTLDKLESIPGFNVIQSPEQMQVLLDQA
GCCIVGQSEQLVPADGILYAARDVTATVDSLPLITASILSKKLVEGLSALVVDVKFGGAA
VFPNQEQARELAKTLVGVGASLGLRVAAALTAMDKPLGRCVGHALEVEEALLCMDGAGPP
DLRDLVTTLGGALLWLSGHAGTQAQGAARVAAALDDGSALGRFERMLAAQGVDPGLARAL
CSGSPAERRQLLPRAREQEELLAPADGTVELVRALPLALVLHELGAGRSRAGEPLRLGVG
AELLVDVGQRLRRGTPWLRVHRDGPALSGPQSRALQEALVLSDRAPFAAPSPFAELVLPP
QQ
Drug Target 1 [top]
Target 1 ID 359
Target 1 Name Thymidylate synthase
Target 1 Synonyms
  1. EC 2.1.1.45
  2. TS
  3. TSase
Target 1 Gene Name TYMS
Target 1 Protein Sequence >Thymidylate synthase 
PVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFGM
QARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDSL
GFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMCA
WNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHIT
GLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEGY
NPHPTIKMEMAV
Target 1 Number of Residues 317
Target 1 Molecular Weight 35585
Target 1 Theoretical pI 7.00
Target 1 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 1 General Function Nucleotide transport and metabolism
Target 1 Specific Function Not Available
Target 1 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 1 Reactions
  • 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 37479 Link Image
Target 1 UniProtKB/Swiss-Prot ID P04818 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name TYSY_HUMAN Link Image
Target 1 PDB ID 1JUJ Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location Not Available
Target 1 Gene Sequence >942 bp 
ATGCCTGTGGCCGGCTCGGAGCTGCCGCGCCGGCCCTTGCCCCCCGCCGCACAGGAGCGG
GACGCCGAGCCGCGTCCGCCGCACGGGGAGCTGCAGTACCTGGGGCAGATCCAACACATC
CTCCGCTGCGGCGTCAGGAAGGACGACCGCACGGGCACCGGCACCCTGTCGGTATTCGGC
ATGCAGGCGCGCTACAGCCTGAGAGATGAATTCCCTCTGCTGACAACCAAACGTGTGTTC
TGGAAGGGTGTTTTGGAGGAGTTGCTGTGGTTTATCAAGGGATCCACAAATGCTAAAGAG
CTGTCTTCCAAGGGAGTGAAAATCTGGGATGCCAATGGATCCCGAGACTTTTTGGACAGC
CTGGGATTCTCCACCAGAGAAGAAGGGGACTTGGGCCCAGTTTATGGCTTCCAGTGGAGG
CATTTTGGGGCAGAATACAGAGATATGGAATCAGATTATTCAGGACAGGGAGTTGACCAA
CTGCAAAGAGTGATTGACACCATCAAAACCAACCCTGACGACAGAAGAATCATCATGTGC
GCTTGGAATCCAAGAGATCTTCCTCTGATGGCGCTGCCTCCATGCCATGCCCTCTGCCAG
TTCTATGTGGTGAACAGTGAGCTGTCCTGCCAGCTGTACCAGAGATCGGGAGACATGGGC
CTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCACGTACATGATTGCGCACATC
ACGGGCCTGAAGCCAGGTGACTTTATACACACTTTGGGAGATGCACATATTTACCTGAAT
CACATCGAGCCACTGAAAATTCAGCTTCAGCGAGAACCCAGACCTTTCCCAAAGCTCAGG
ATTCTTCGAAAAGTTGAGAAAATTGATGACTTCAAAGCTGAAGACTTTCAGATTGAAGGG
TACAATCCGCATCCAACTATTAAAATGGAAATGGCTGTTTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID TYMS Link Image
Target 1 GenAtlas ID TYMS Link Image
Target 1 HGNC ID HGNC:12441 Link Image
Target 1 Chromosome Location 18
Target 1 Locus 18p11.32
Target 1 SNPs SNPJam Report Link Image
Target 1 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 1 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]
  2. Formentini A, Sander S, Denzer S, Straeter J, Henne-Bruns D, Kornmann M: Thymidylate synthase expression in resectable and unresectable pancreatic cancer: role as predictive or prognostic marker? Int J Colorectal Dis. 2007 Jan;22(1):49-55. Epub 2006 Mar 15. [PubMed Link Image]
  3. Huang CL, Yokomise H, Fukushima M, Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2006 Apr;2(2):289-99. [PubMed Link Image]
  4. Fernandez-Contreras ME, Sanchez-Prudencio S, Sanchez-Hernandez JJ, Garcia de Paredes ML, Gisbert JP, Roda-Navarro P, Gamallo C: Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil. Int J Oncol. 2006 May;28(5):1303-10. [PubMed Link Image]
  5. Garcia V, Garcia JM, Pena C, Silva J, Dominguez G, Hurtado A, Alonso I, Rodriguez R, Provencio M, Bonilla F: Thymidylate synthase messenger RNA expression in plasma from patients with colon cancer: prognostic potential. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2095-100. [PubMed Link Image]
  6. Ploylearmsaeng SA, Fuhr U, Jetter A: How may anticancer chemotherapy with fluorouracil be individualised? Clin Pharmacokinet. 2006;45(6):567-92. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 2257
Target 2 Name Uridine phosphorylase
Target 2 Synonyms
  1. EC 2.4.2.3
  2. UPase
  3. UrdPase
Target 2 Gene Name udp
Target 2 Protein Sequence >Uridine phosphorylase 
MSKSDVFHLGLTKNDLQGATLAIVPGDPDRVEKIAALMDKPVKLASHREFTTWRAELDGK
PVIVCSTGIGGPSTSIAVEELAQLGIRTFLRIGTTGAIQPHINVGDVLVTTASVRLDGAS
LHFAPLEFPAVADFECTTALVEAAKSIGATTHVGVTASSDTFYPGQERYDTYSGRVVRHF
KGSMEEWQAMGVMNYEMESATLLTMCASQGLRAGMVAGVIVNRTQQEIPNAETMKQTESH
AVKIVVEAARRLL
Target 2 Number of Residues 257
Target 2 Molecular Weight 27159
Target 2 Theoretical pI 6.16
Target 2 GO Classification
Function
transferase activity
transferase activity, transferring glycosyl groups
transferase activity, transferring pentosyl groups
uridine phosphorylase activity
catalytic activity
Process
nucleotide metabolism
nucleotide catabolism
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleoside metabolism
Component
cell
intracellular
cytoplasm
Target 2 General Function Nucleotide transport and metabolism
Target 2 Specific Function Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1- phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis
Target 2 Pathways
Name SMPDB Link KEGG Link
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 2 Reactions
  • uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Essential
Target 2 GenBank ID Protein 43242 Link Image
Target 2 UniProtKB/Swiss-Prot ID P12758 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name UDP_ECOLI Link Image
Target 2 PDB ID 1T0U Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasm
Target 2 Gene Sequence >762 bp 
ATGTCCAAGTCTGATGTTTTTCATCTCGGCCTCACTAAAAACGATTTACAAGGGGCTACG
CTTGCCATCGTCCCTGGCGACCCGGATCGTGTGGAAAAGATCGCCGCGCTGATGGATAAG
CCGGTTAAGCTGGCATCTCACCGCGAATTCACTACCTGGCGTGCAGAGCTGGATGGTAAA
CCTGTTATCGTCTGCTCTACCGGTATCGGCGGCCCGTCTACCTCTATTGCTGTTGAAGAG
CTGGCACAGCTGGGCATTCGCACCTTCCTGCGTATCGGTACAACGGGCGCTATTCAGCCG
CATATTAATGTGGGTGATGTCCTGGTTACCACGGCGTCTGTCCGTCTGGATGGCGCGAGC
CTGCACTTCGCACCGCTGGAATTCCCGGCTGTCGCTGATTTCGAATGTACGACTGCGCTG
GTTGAAGCTGCGAAATCCATTGGCGCGACAACTCACGTTGGCGTGACAGCTTCTTCTGAT
ACCTTCTACCCAGGTCAGGAACGTTACGATACTTACTCTGGTCGCGTAGTTCGTCACTTT
AAAGGTTCTATGGAAGAGTGGCAGGCGATGGGCGTAATGAACTATGAAATGGAATCTGCA
ACCCTGCTGACCATGTGTGCAAGTCAGGGCCTGCGTGCCGGTATGGTAGCGGGTGTTATC
GTTAACCGCACCCAGCAAGAGATCCCGAATGCTGAGACGATGAAACAAACCGAAAGCCAT
GCGGTGAAAATCGTGGTGGAAGCGGCGCGTCGTCTGCTGTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus Not Available
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Burling FT, Kniewel R, Buglino JA, Chadha T, Beckwith A, Lima CD: Structure of Escherichia coli uridine phosphorylase at 2.0 A. Acta Crystallogr D Biol Crystallogr. 2003 Jan;59(Pt 1):73-6. Epub 2002 Dec 19. [PubMed Link Image]
  2. Daniels DL, Plunkett G 3rd, Burland V, Blattner FR: Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes. Science. 1992 Aug 7;257(5071):771-8. [PubMed Link Image]
  3. Walton L, Richards CA, Elwell LP: Nucleotide sequence of the Escherichia coli uridine phosphorylase (udp) gene. Nucleic Acids Res. 1989 Aug 25;17(16):6741. [PubMed Link Image]
  4. Morgunova EYu, Mikhailov AM, Popov AN, Blagova EV, Smirnova EA, Vainshtein BK, Mao C, Armstrong ShR, Ealick SE, Komissarov AA, et al.: Atomic structure at 2.5 A resolution of uridine phosphorylase from E. coli as refined in the monoclinic crystal lattice. FEBS Lett. 1995 Jun 26;367(2):183-7. [PubMed Link Image]
  5. Henzel WJ, Billeci TM, Stults JT, Wong SC, Grimley C, Watanabe C: Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5011-5. [PubMed Link Image]
  6. Gonzalez-Gil G, Bringmann P, Kahmann R: FIS is a regulator of metabolism in Escherichia coli. Mol Microbiol. 1996 Oct;22(1):21-9. [PubMed Link Image]
  7. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-74. [PubMed Link Image]
  8. Veiko VP, Chebotaev DV, Ovcharova IV, Gul'ko LB: [Protein engineering of uridine phosphorylase from Escherichia coli K-12. I. Cloning and expression of uridine phosphorylase genes from Klebsiella aerogenes and Salmonella typhimurium in E. coli] Bioorg Khim. 1998 May;24(5):381-7. [PubMed Link Image]
Target 2 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]
  3. Pritchard RH, Ahmad SI: Fluorouracil and the isolation of mutants lacking uridine phosphorylase in Escherichia coli: location of the gene. Mol Gen Genet. 1971;111(1):84-8. [PubMed Link Image]
  4. Grem JL, van Groeningen CJ, Ismail AA, Johnston PG, Alexander HR, Allegra CJ: The role of interferon-alpha as a modulator of fluorouracil and leucovorin. Eur J Cancer. 1995 Jul-Aug;31A(7-8):1316-20. [PubMed Link Image]
  5. Liu M, Cao D, Russell R, Handschumacher RE, Pizzorno G: Expression, characterization, and detection of human uridine phosphorylase and identification of variant uridine phosphorolytic activity in selected human tumors. Cancer Res. 1998 Dec 1;58(23):5418-24. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 2412
Target 3 Name Uracil phosphoribosyltransferase
Target 3 Synonyms
  1. EC 2.4.2.9
  2. UMP pyrophosphorylase
  3. UPRT
  4. UPRTase
Target 3 Gene Name Not Available
Target 3 Protein Sequence >Uracil phosphoribosyltransferase 
MAQVPASGKLLVDPRYSTNDQEESILQDIITRFPNVVLMKQTAQLRAMMTIIRDKETPKE
EFVFYADRLIRLLIEEALNELPFEKKEVTTPLDVSYHGVSFYSKICGVSIVRAGESMESG
LRAVCRGCRIGKILIQRDETTAEPKLIYEKLPADIRDRWVMLLDPMCATAGSVCKAIEVL
LRLGVKEERIIFVNILAAPQGIERVFKEYPKVRMVTAAVDICLNSRYYIVPGIGDFGDRY
FGTM
Target 3 Number of Residues 248
Target 3 Molecular Weight 27647
Target 3 Theoretical pI 7.06
Target 3 GO Classification
Function
Not Available
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleoside metabolism
Component
Not Available
Target 3 General Function Nucleotide transport and metabolism
Target 3 Specific Function UMP + diphosphate = uracil + 5-phospho-alpha- D-ribose 1-diphosphate
Target 3 Pathways
Name SMPDB Link KEGG Link
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 3 Reactions
  • UMP + diphosphate = uracil + 5-phospho-alpha-D-ribose 1-diphosphate
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Essential
Target 3 GenBank ID Protein 499106 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q26998 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name UPP_TOXGO Link Image
Target 3 PDB ID 1JLR Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >735 bp 
ATGGCGCAGGTCCCAGCGAGCGGAAAGCTCCTTGTCGATCCCCGATATTCGACAAACGAC
CAGGAAGAAAGCATTCTCCAGGACATCATCACGAGGTTTCCCAATGTGGTGCTCATGAAG
CAGACGGCTCAGCTTCGAGCGATGATGACCATCATTCGTGATAAAGAAACACCGAAGGAA
GAATTCGTCTTCTACGCCGACCGCCTGATTCGCCTCCTCATCGAAGAAGCTTTGAACGAA
CTGCCGTTCGAAAAGAAGGAAGTGACAACCCCTCTGGATGTGTCATACCATGGAGTTTCC
TTTTATTCCAAGATCTGTGGCGTCTCGATTGTGAGAGCTGGCGAGTCGATGGAAAGTGGC
TTGCGGGCAGTTTGCCGCGGCTGCCGCATCGGGAAAATCCTCATCCAGAGAGACGAAACA
ACTGCGGAGCCTAAGCTGATCTACGAGAAGCTGCCTGCCGACATTAGAGATCGCTGGGTG
ATGCTGCTCGATCCGATGTGCGCGACGGCGGGCAGTGTGTGCAAAGCGATCGAGGTCCTC
CTGAGGCTCGGCGTGAAGGAAGAGAGAATCATTTTCGTCAACATTTTGGCTGCTCCCCAA
GGCATTGAACGTGTTTTCAAGGAATACCCGAAAGTCCGCATGGTCACTGCTGCTGTTGAC
ATCTGCCTGAACTCGAGGTACTACATCGTCCCCGGCATTGGTGATTTCGGTGACCGGTAC
TTTGGAACCATGTAG
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 Not Available
Target 3 Locus Not Available
Target 3 SNPs Not Available
Target 3 General References
  1. Carter D, Donald RG, Roos D, Ullman B: Expression, purification, and characterization of uracil phosphoribosyltransferase from Toxoplasma gondii. Mol Biochem Parasitol. 1997 Aug;87(2):137-44. [PubMed Link Image]
  2. Schumacher MA, Carter D, Scott DM, Roos DS, Ullman B, Brennan RG: Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding. EMBO J. 1998 Jun 15;17(12):3219-32. [PubMed Link Image]
Target 3 Drug References
  1. Breuner A, Brondsted L, Hammer K: Novel organization of genes involved in prophage excision identified in the temperate lactococcal bacteriophage TP901-1. J Bacteriol. 1999 Dec;181(23):7291-7. [PubMed Link Image]
  2. Lauer B, Russwurm R, Bormann C: Molecular characterization of two genes from Streptomyces tendae Tu901 required for the formation of the 4-formyl-4-imidazolin-2-one-containing nucleoside moiety of the peptidyl nucleoside antibiotic nikkomycin. Eur J Biochem. 2000 Mar;267(6):1698-706. [PubMed Link Image]
  3. 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]
  4. 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]
  5. Bohne W, Roos DS: Stage-specific expression of a selectable marker in Toxoplasma gondii permits selective inhibition of either tachyzoites or bradyzoites. Mol Biochem Parasitol. 1997 Sep;88(1-2):115-26. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 2479
Target 4 Name Dihydropyrimidine dehydrogenase [NADP+]
Target 4 Synonyms
  1. DHPDHase
  2. DPD
  3. Dihydropyrimidine dehydrogenase precursor
  4. Dihydrothymine dehydrogenase
  5. Dihydrouracil dehydrogenase
  6. EC 1.3.1.2
Target 4 Gene Name DPYD
Target 4 Protein Sequence >Dihydropyrimidine dehydrogenase [NADP+] precursor 
MAPVLSKDVADIESILALNPRTQSHAALHSTLAKKLDKKHWKRNPDKNCFHCEKLENNFG
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTHLDIKSFITSISNKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGSINIGGLQQFASEVFKAMNIPQIRNPCLPSQE
KMPEAYSAKIALLGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSENEITLNTLKEEGYKAAFIGIGLPEPKTDDIFQGLTQD
QGFYTSKDFLPLVAKSSKAGMCACHSPLPSIRGAVIVLGAGDTAFDCATSALRCGARRVF
LVFRKGFVNIRAVPEEVELAKEEKCEFLPFLSPRKVIVKGGRIVAVQFVRTEQDETGKWN
EDEDQIVHLKADVVISAFGSVLRDPKVKEALSPIKFNRWDLPEVDPETMQTSEPWVFAGG
DIVGMANTTVESVNDGKQASWYIHKYIQAQYGASVSAKPELPLFYTPVDLVDISVEMAGL
KFINPFGLASAAPTTSSSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIVRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWMELSRKAEAS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGADGVTATNTVSGLMGLKADGTPWPAVGAGKRTTYGGVSGTAIRPIALRAVTT
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAVQNQDFTVIQDYCTGLKALLYL
KSIEELQGWDGQSPGTESHQKGKPVPRIAELMGKKLPNFGPYLEQRKKIIAEEKMRLKEQ
NAAFPPLERKPFIPKKPIPAIKDVIGKALQYLGTFGELSNIEQVVAVIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTVTDTCTGCTLCLSVCPIIDCIRMVSRTTPYEPKRGLPLA
VNPVC
Target 4 Number of Residues 1042
Target 4 Molecular Weight 111425
Target 4 Theoretical pI 6.78
Target 4 GO Classification
Function
disulfide oxidoreductase activity
dihydroorotate dehydrogenase activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on the CH-CH group of donors
oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor
dihydroorotate oxidase activity
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
transporter activity
electron transporter activity
Process
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleobase metabolism
pyrimidine base metabolism
pyrimidine base biosynthesis
'de novo' pyrimidine base biosynthesis
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
membrane
cell
intracellular
cytoplasm
Target 4 General Function Amino acid transport and metabolism
Target 4 Specific Function Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine
Target 4 Pathways
Name SMPDB Link KEGG Link
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 4 Reactions
  • 5,6-dihydrouracil + NADP+ = uracil + NADPH + H+
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Essential
Target 4 GenBank ID Protein 558307 Link Image
Target 4 UniProtKB/Swiss-Prot ID Q28943 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name DPYD_PIG Link Image
Target 4 PDB ID 1GTE Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Cytoplasm
Target 4 Gene Sequence >3078 bp 
ATGGCCCCTGTGCTGAGCAAGGACGTGGCGGACATCGAGAGTATCCTGGCTTTAAATCCT
CGAACACAGTCTCATGCAGCCCTTCATTCCACTTTGGCCAAGAAATTGGATAAGAAACAC
TGGAAAAGAAATCCCGATAAGAACTGCTTTCATTGCGAGAAGCTGGAGAATAATTTTGGT
GACATCAAGCACACGACTCTTGGTGAGCGAGGAGCTCTCCGAGAAGCAATGAGATGCCTG
AAATGTGCCGATGCTCCCTGTCAGAAGAGCTGTCCAACTCATCTAGATATCAAATCATTC
ATCACAAGTATCTCAAATAAGAACTATTATGGAGCTGCTAAGATGATTTTTTCTGACAAC
CCTCTTGGTCTGACCTGTGGAATGGTATGTCCAACCTCTGATCTTTGTGTAGGAGGATGC
AATTTATATGCAACTGAAGAGGGATCAATTAATATTGGTGGATTGCAGCAGTTTGCTTCT
GAGGTGTTCAAAGCAATGAATATCCCACAAATCAGGAATCCTTGTCTGCCATCCCAAGAG
AAAATGCCTGAAGCTTATTCTGCAAAGATTGCTCTTTTGGGTGCTGGGCCTGCAAGTATA
AGCTGTGCTTCCTTCTTGGCTCGATTAGGCTACTCTGACATCACTATATTTGAAAAACAA
GAATATGTTGGTGGTTTAAGTACTTCTGAAATCCCTCAGTTCCGGCTGCCATATGATGTA
GTGAATTTTGAGATTGAGCTTATGAAGGACCTTGGTGTAAAGATAATTTGTGGTAAAAGC
CTTTCAGAGAATGAAATTACTCTCAACACTTTAAAAGAAGAAGGGTATAAAGCTGCTTTC
ATTGGTATAGGTTTGCCAGAACCCAAAACGGATGACATCTTCCAAGGCCTGACACAGGAC
CAGGGGTTTTACACATCCAAAGACTTTCTGCCCCTTGTAGCCAAAAGCAGTAAAGCAGGA
ATGTGTGCCTGTCACTCTCCATTGCCATCGATACGGGGAGCCGTGATTGTACTCGGAGCT
GGAGACACAGCTTTCGACTGTGCAACATCCGCTTTACGTTGTGGAGCCCGCCGAGTGTTC
CTCGTCTTCAGAAAAGGCTTTGTTAATATAAGAGCTGTCCCTGAGGAGGTGGAGCTTGCT
AAGGAAGAAAAATGTGAATTTTTGCCTTTCCTGTCCCCACGGAAGGTTATAGTTAAAGGT
GGGAGAATTGTTGCCGTGCAATTTGTTCGAACAGAACAAGATGAAACTGGAAAATGGAAT
GAAGATGAAGATCAGATAGTCCATCTGAAGGCTGATGTGGTCATCAGTGCCTTTGGCTCA
GTGCTGAGGGATCCTAAAGTAAAAGAAGCCTTGAGCCCTATAAAATTTAACAGATGGGAT
CTCCCAGAAGTAGATCCAGAAACTATGCAAACCAGTGAACCATGGGTGTTTGCAGGTGGT
GATATCGTTGGTATGGCTAACACTACGGTGGAATCCGTAAATGACGGAAAGCAGGCCTCC
TGGTACATTCACAAATATATCCAGGCCCAATATGGAGCTTCAGTTTCTGCCAAGCCCGAA
CTGCCCCTGTTTTATACGCCTGTTGACCTGGTGGACATCAGCGTGGAAATGGCTGGATTA
AAGTTTATAAATCCTTTTGGTCTTGCCAGTGCAGCTCCAACTACCAGTTCATCGATGATT
CGAAGAGCTTTTGAAGCTGGATGGGGTTTTGCCCTGACCAAAACTTTCTCTCTTGATAAG
GACATAGTGACAAATGTCTCACCCAGAATCGTCCGGGGGACTACCTCTGGCCCCATGTAC
GGCCCTGGACAAAGCTCCTTCCTGAATATTGAGCTCATCAGTGAAAAAACAGCTGCATAT
TGGTGTCAAAGTGTCACTGAACTAAAAGCTGACTTTCCAGACAATATTGTGATCGCCAGC
ATCATGTGTAGTTACAACAAAAATGACTGGATGGAACTCTCCAGAAAGGCTGAGGCCTCT
GGAGCAGATGCCTTGGAGTTAAATCTGTCATGTCCACACGGCATGGGAGAAAGAGGAATG
GGCCTGGCTTGTGGGCAGGATCCAGAGCTGGTGCGGAACATCTGTCGCTGGGTTAGGCAA
GCTGTTCAGATTCCCTTTTTTGCCAAGTTGACCCCAAACGTCACTGATATAGTAAGCATC
GCCAGAGCGGCCAAGGAAGGTGGCGCAGATGGTGTTACAGCCACCAACACGGTCTCAGGT
CTCATGGGATTAAAAGCCGATGGCACGCCCTGGCCAGCGGTGGGTGCTGGCAAGCGGACT
ACATACGGAGGAGTGTCTGGCACGGCCATCAGACCAATTGCTTTGAGAGCTGTGACCACC
ATTGCTCGTGCTTTGCCTGGATTTCCCATTTTGGCTACTGGTGGAATTGACTCAGCTGAA
AGTGGACTTCAGTTTCTCCACAGTGGTGCTTCGGTCCTCCAGGTATGCAGTGCTGTTCAG
AATCAGGATTTCACTGTCATCCAAGACTATTGCACTGGCCTCAAAGCCTTGCTTTATCTG
AAAAGCATTGAAGAACTACAAGGCTGGGATGGGCAGAGTCCAGGTACCGAGAGTCACCAG
AAGGGGAAACCAGTTCCTCGTATTGCTGAACTCATGGGAAAGAAACTGCCAAATTTTGGA
CCTTATCTGGAGCAACGCAAGAAAATCATAGCAGAGGAAAAGATGAGACTGAAAGAACAA
AATGCAGCTTTTCCACCACTTGAGAGAAAACCTTTTATTCCCAAAAAGCCTATTCCTGCT
ATTAAGGATGTAATTGGAAAAGCACTGCAGTACCTTGGAACGTTTGGTGAACTGAGCAAC
ATAGAGCAAGTTGTGGCTGTGATCGATGAAGAAATGTGTATCAACTGTGGCAAATGCTAC
ATGACCTGTAATGACTCTGGCTACCAGGCTATCCAGTTTGATCCCGAAACCCACCTGCCC
ACCGTTACTGACACTTGCACAGGCTGTACCCTGTGTCTCTCCGTCTGCCCTATTATCGAC
TGCATCAGAATGGTTTCCAGGACAACACCTTACGAACCAAAGAGAGGCTTGCCCTTGGCT
GTGAATCCGGTGTGCTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID Not Available
Target 4 GenAtlas ID Not Available
Target 4 HGNC ID Not Available
Target 4 Chromosome Location Not Available
Target 4 Locus Not Available
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Yokota H, Fernandez-Salguero P, Furuya H, Lin K, McBride OW, Podschun B, Schnackerz KD, Gonzalez FJ: cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria. J Biol Chem. 1994 Sep 16;269(37):23192-6. [PubMed Link Image]
Target 4 Drug References
  1. Bosch TM, Meijerman I, Beijnen JH, Schellens JH: Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin Pharmacokinet. 2006;45(3):253-85. [PubMed Link Image]
  2. 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]
  3. 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]
  4. Bosch TM, Bakker R, Schellens JH, Cats A, Smits PH, Beijnen JH: Rapid detection of the DPYD IVS14+1G>A mutation for screening patients to prevent fluorouracil-related toxicity. Mol Diagn Ther. 2007;11(2):105-8. [PubMed Link Image]
  5. Keizer HJ, De Bruijn EA, Tjaden UR, De Clercq E: Inhibition of fluorouracil catabolism in cancer patients by the antiviral agent (E)-5-(2-bromovinyl)-2'-deoxyuridine. J Cancer Res Clin Oncol. 1994;120(9):545-9. [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.