Drugbank Logo

Showing drug card for Capecitabine (DB01101)

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 16:04:48
Primary Accession Number DB01101
Secondary Accession Number
  • APRD00203
Name Capecitabine
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.
Synonyms
  1. R340
  2. capecitabine
Brand Names
  1. Xeloda
Brand Mixtures Not Available
Chemical IUPAC Name pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate
Chemical Formula C15H22FN3O6
Chemical Structure Structure
CAS Registry Number 154361-50-9
InChI Identifier InChI=1/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1/f/h18H
InChI Key GAGWJHPBXLXJQN-WSDNTSAQDY
KEGG Drug D01223 Link Image
KEGG Compound C12650 Link Image
PubChem Compound 60953 Link Image
PubChem Substance 197173 Link Image
ChEBI ID Not Available
PharmGKB ID PA448771 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02238454 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/capecitabine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Capecitabine Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 359.3501
Monoisotopic Molecular Weight 359.1493
State Solid
Melting Point 110-121 oC
Experimental Water Solubility 26 mg/mL Source: PhysProp
Predicted Water Solubility 2.48e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.4 Source: PhysProp
Predicted LogP 1.17 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.16 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
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 CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
Canonical SMILES CCCCCOC(=O)NC1=NC(=O)N(C=C1F)C1OC(C)C(O)C1O
Drug Category
  • Antimetabolites
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Prodrugs
ATC Codes
AHFS Codes
  • 10:00.00
Indication For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen.
Pharmacology Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of patients with metastatic breast cancer. It is an orally administered systemic prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) which is converted to 5-fluorouracil.
Mechanism of Action Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. FdUMP inhibits DNA synthesis by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.3 The active moiety of capecitabine, fluorouracil, is cell cycle phase-specific (Sphase). Both normal and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division. Second nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.
Absorption Not Available
Toxicity Not Available
Protein Binding < 60%
Biotransformation Metabolized by thymidine phosphorylase to fluoruracil.
Half Life 0.75 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The antineoplastic agent increases the anticoagulant effect
Anisindione The antineoplastic agent increases the anticoagulant effect
Dicumarol The antineoplastic agent increases the anticoagulant effect
Ethotoin Capecitabine increases the effect of hydantoin
Fosphenytoin Capecitabine increases the effect of hydantoin
Mephenytoin Capecitabine increases the effect of hydantoin
Phenytoin Capecitabine increases the effect of hydantoin
Warfarin The antineoplastic agent increases the anticoagulant effect
Food Interactions
  • Take 12 hours apart, within 30 minutes of the end of breakfast and dinner to reduce nausea.
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. Cytidine deaminase
  2. Thymidine phosphorylase
Targets
  1. Thymidylate synthase
  2. Dihydropyrimidine dehydrogenase [NADP+]
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytidine deaminase
Enzyme 1 Gene Name CDA
Enzyme 1 SwissProt ID P32320 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P32320|CDD_HUMAN Cytidine deaminase (EC 3.5.4.5) 
MAQKRPACTLKPECVQQLLVCSQEAKKSAYCPYSHFPVGAALLTQEGRIFKGCNIENACY
PLGICAERTAIQKAVSEGYKDFRAIAIASDMQDDFISPCGACRQVMREFGTNWPVYMTKP
DGTYIVMTVQELLPSSFGPEDLQKTQ
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. Patel A, Pluim T, Helms A, Bauer A, Tuttle RM, Francis GL: Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults. Cancer Chemother Pharmacol. 2004 May;53(5):409-14. [PubMed Link Image]
  2. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. [PubMed Link Image]
  3. Carlini LE, Meropol NJ, Bever J, Andria ML, Hill T, Gold P, Rogatko A, Wang H, Blanchard RL: UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36. [PubMed Link Image]
  4. Li KM, Rivory LP, Clarke SJ: Rapid quantitation of plasma 2'-deoxyuridine by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry and its application to pharmacodynamic studies in cancer patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jun 5;820(1):121-30. Epub 2005 Apr 19. [PubMed Link Image]
  5. Fischel JL, Ciccolini J, Formento P, Ferrero JM, Milano G: Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5'-deoxyuridine. Anticancer Drugs. 2006 Aug;17(7):807-13. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1302
Target 2 Name Dihydropyrimidine dehydrogenase [NADP+]
Target 2 Synonyms
  1. DHPDHase
  2. DPD
  3. Dihydropyrimidine dehydrogenase precursor
  4. Dihydrothymine dehydrogenase
  5. Dihydrouracil dehydrogenase
  6. EC 1.3.1.2
Target 2 Gene Name DPYD
Target 2 Protein Sequence >Dihydropyrimidine dehydrogenase [NADP+] precursor 
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE
KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD
QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF
IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN
EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG
DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL
KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL
KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ
NVAFSPLKRSCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS
VNPVC
Target 2 Number of Residues 1042
Target 2 Molecular Weight 111375
Target 2 Theoretical pI 7.05
Target 2 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 2 General Function Amino acid transport and metabolism
Target 2 Specific Function Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil
Target 2 Pathways
Name SMPDB Link KEGG Link
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 2 Reactions
  • 5,6-dihydrouracil + NADP+ = uracil + NADPH + H+
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 558305 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q12882 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name DPYD_HUMAN Link Image
Target 2 PDB ID 1GTE Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasm
Target 2 Gene Sequence >3078 bp 
ATGGCCCCTGTGCTCAGTAAGGACTCGGCGGACATCGAGAGTATCCTGGCTTTAAATCCT
CGAACACAAACTCATGCAACTCTGTGTTCCACTTCGGCCAAGAAATTAGACAAGAAACAT
TGGAAAAGAAATCCTGATAAGAACTGCTTTAATTGTGAGAAGCTGGAGAATAATTTTGAT
GACATCAAGCACACGACTCTTGGTGAGCGAGGAGCTCTCCGAGAAGCAATGAGATGCCTG
AAATGTGCAGATGCCCCGTGTCAGAAGAGCTGTCCAACTAATCTTGATATTAAATCATTC
ATCACAAGTATTGCAAACAAGAACTATTATGGAGCTGCTAAGATGATATTTTCTGACAAC
CCACTTGGTCTGACTTGTGGAATGGTATGTCCAACCTCTGATCTATGTGTAGGTGGATGC
AATTTATATGCCACTGAAGAGGGACCCATTAATATTGGTGGATTGCAGCAATTTGCTACT
GAGGTATTCAAAGCAATGAGTATCCCACAGATCAGAAATCCTTCGCTGCCTCCCCCAGAA
AAAATGTCTGAAGCCTATTCTGCAAAGATTGCTCTTTTTGGTGCTGGGCCTGCAAGTATA
AGTTGTGCTTCCTTTTTGGCTCGATTGGGGTACTCTGACATCACTATATTTGAAAAACAA
GAATATGTTGGTGGTTTAAGTACTTCTGAAATTCCTCAGTTCCGGCTGCCGTATGATGTA
GTGAATTTTGAGATTGAGCTAATGAAGGACCTTGGTGTAAAGATAATTTGCGGTAAAAGC
CTTTCAGTGAATGAAATGACTCTTAGCACTTTGAAAGAAAAAGGCTACAAAGCTGCTTTC
ATTGGAATAGGTTTGCCAGAACCCAATAAAGATGCCATCTTCCAAGGCCTGACGCAGGAC
CAGGGGTTTTATACATCCAAAGACTTTTTGCCACTTGTAGCCAAAGGCAGTAAAGCAGGA
ATGTGCGCCTGTCACTCTCCATTGCCATCGATACGGGGAGTCGTGATTGTACTTGGAGCT
GGAGACACTGCCTTCGACTGTGCAACATCTGCTCTACGTTGTGGAGCTCGCCGAGTGTTC
ATCGTCTTCAGAAAAGGCTTTGTTAATATAAGAGCTGTCCCTGAGGAGATGGAGCTTGCT
AAGGAAGAAAAGTGTGAATTTCTGCCATTCCTGTCCCCACGGAAGGTTATAGTAAAAGGT
GGGAGAATTGTTGCTATGCAGTTTGTTCGGACAGAGCAAGATGAAACTGGAAAATGGAAT
GAAGATGAAGATCAGATGGTCCATCTGAAAGCCGATGTGGTCATCAGTGCCTTTGGTTCA
GTTCTGAGTGATCCTAAAGTAAAAGAAGCCTTGAGCCCTATAAAATTTAACAGATGGGGT
CTCCCAGAAGTAGATCCAGAAACTATGCAAACTAGTGAAGCATGGGTATTTGCAGGTGGT
GATGTCGTTGGTTTGGCTAACACTACAGTGGAATCGGTGAATGATGGAAAGCAAGCTTCT
TGGTACATTCACAAATACGTACAGTCACAATATGGAGCTTCCGTTTCTGCCAAGCCTGAA
CTACCCCTCTTTTACACTCCTATTGATCTGGTGGACATTAGTGTAGAAATGGCCGGATTG
AAGTTTATAAATCCTTTTGGTCTTGCTAGCGCAACTCCAGCCACCAGCACATCAATGATT
CGAAGAGCTTTTGAAGCTGGATGGGGTTTTGCCCTCACCAAAACTTTCTCTCTTGATAAG
GACATTGTGACAAATGTTTCCCCCAGAATCATCCGGGGAACCACCTCTGGCCCCATGTAT
GGCCCTGGACAAAGCTCCTTTCTGAATATTGAGCTCATCAGTGAGAAAACGGCTGCATAT
TGGTGTCAAAGTGTCACTGAACTAAAGGCTGACTTCCCAGACAACATTGTGATTGCTAGC
ATTATGTGCAGTTACAATAAAAATGACTGGACGGAACTTGCCAAGAAGTCTGAGGATTCT
GGAGCAGATGCCCTGGAGTTAAATTTATCATGTCCACATGGCATGGGAGAAAGAGGAATG
GGCCTGGCCTGTGGGCAGGATCCAGAGCTGGTGCGGAACATCTGCCGCTGGGTTAGGCAA
GCTGTTCAGATTCCTTTTTTTGCCAAGCTGACCCCAAATGTCACTGATATTGTGAGCATC
GCAAGAGCTGCAAAGGAAGGTGGTGCCAATGGCGTTACAGCCACCAACACTGTCTCAGGT
CTGATGGGATTAAAATCTGATGGCACACCTTGGCCAGCAGTGGGGATTGCAAAGCGAACT
ACATATGGAGGAGTGTCTGGGACAGCAATCAGACCTATTGCTTTGAGAGCTGTGACCTCC
ATTGCTCGTGCTCTGCCTGGATTTCCCATTTTGGCTACTGGTGGAATTGACTCTGCTGAA
AGTGGTCTTCAGTTTCTCCATAGTGGTGCTTCCGTCCTCCAGGTATGCAGTGCCATTCAG
AATCAGGATTTCACTGTGATCGAAGACTACTGCACTGGCCTCAAAGCCCTGCTTTATCTG
AAAAGCATTGAAGAACTACAAGACTGGGATGGACAGAGTCCAGCTACTGTGAGTCACCAG
AAAGGGAAACCAGTTCCACGTATAGCTGAACTCATGGACAAGAAACTGCCAAGTTTTGGA
CCTTATCTGGAACAGCGCAAGAAAATCATAGCAGAAAACAAGATTAGACTGAAAGAACAA
AATGTAGCTTTTTCACCACTTAAGAGAAGCTGTTTTATCCCCAAAAGGCCTATTCCTACC
ATCAAGGATGTAATAGGAAAAGCACTGCAGTACCTTGGAACATTTGGTGAATTGAGCAAC
GTAGAGCAAGTTGTGGCTATGATTGATGAAGAAATGTGTATCAACTGTGGTAAATGCTAC
ATGACCTGTAATGATTCTGGCTACCAGGCTATACAGTTTGATCCAGAAACCCACCTGCCC
ACCATAACCGACACTTGTACAGGCTGTACTCTGTGTCTCAGTGTTTGCCCTATTGTCGAC
TGCATCAAAATGGTTTCCAGGACAACACCTTATGAACCAAAGAGAGGCGTACCCTTATCT
GTGAATCCGGTGTGTTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID DPYD Link Image
Target 2 GenAtlas ID DPYD Link Image
Target 2 HGNC ID HGNC:3012 Link Image
Target 2 Chromosome Location 1
Target 2 Locus 1p22
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Lu ZH, Zhang R, Diasio RB: Purification and characterization of dihydropyrimidine dehydrogenase from human liver. J Biol Chem. 1992 Aug 25;267(24):17102-9. [PubMed Link Image]
  2. 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]
  3. Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH: A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. J Inherit Metab Dis. 1996;19(5):645-54. [PubMed Link Image]
  4. Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB: Structural organization of the human dihydropyrimidine dehydrogenase gene. Cancer Res. 1997 May 1;57(9):1660-3. [PubMed Link Image]
  5. Fernandez-Salguero PM, Sapone A, Wei X, Holt JR, Jones S, Idle JR, Gonzalez FJ: Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin. Pharmacogenetics. 1997 Apr;7(2):161-3. [PubMed Link Image]
  6. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH: Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene. J Inherit Metab Dis. 1997 Jul;20(3):335-8. [PubMed Link Image]
  7. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH: Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet. 1997 Dec;101(3):333-8. [PubMed Link Image]
  8. Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T: Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine. Cancer Lett. 1998 Jan 9;122(1-2):107-13. [PubMed Link Image]
Target 2 Drug References
  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed Link Image]
  2. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y: A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202. [PubMed Link Image]
  3. Blanquicett C, Gillespie GY, Nabors LB, Miller CR, Bharara S, Buchsbaum DJ, Diasio RB, Johnson MR: Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45. [PubMed Link Image]
  4. Gross E, Seck K, Neubauer S, Mayr J, Hellebrand H, Ratanaphan A, Lutz V, Stockinger H, Kiechle M: High-throughput genotyping by DHPLC of the dihydropyrimidine dehydrogenase gene implicated in (fluoro)pyrimidine catabolism. Int J Oncol. 2003 Feb;22(2):325-32. [PubMed Link Image]
  5. Endo M, Miwa M, Eda H, Ura M, Tanimura H, Ishikawa T, Miyazaki-Nose T, Hattori K, Shimma N, Yamada-Okabe H, Ishitsuka H: Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805. [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.