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Record Information
Version2.0
Creation Date2009-07-30 17:58:54 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3507
Identification
Common NameCapecitabine
ClassSmall Molecule
DescriptionCapecitabine 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 fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.
Compound Type
  • Amine
  • Antimetabolite
  • Antimetabolite, Antineoplastic
  • Antineoplastic Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Prodrug
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(1-(5-Deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-carbamic acid pentyl ester
Capecitabin
Capecitabina
Capecitabinum
Pentyl 1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamate
Pentyl [1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate
R340
Xeloda
Chemical FormulaC15H22FN3O6
Average Molecular Mass359.350 g/mol
Monoisotopic Mass359.149 g/mol
CAS Registry Number154361-50-9
IUPAC Namepentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate
Traditional Namecapecitabine
SMILES[H][C@]1(C)O[C@@]([H])(N2C=C(F)C(N=C(O)OCCCCC)=NC2=O)[C@]([H])(O)[C@]1([H])O
InChI IdentifierInChI=1S/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
InChI KeyInChIKey=GAGWJHPBXLXJQN-UORFTKCHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 5'-deoxyribonucleosides. These are nucleosides in which the oxygen atom at the 5'position of the ribose moiety has been replaced by another atom. The nucleobases here are limited to purine, pyrimidine, and pyridine derivatives.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
Class5'-deoxyribonucleosides
Sub ClassNot Available
Direct Parent5'-deoxyribonucleosides
Alternative Parents
Substituents
  • 5'-deoxyribonucleoside
  • Glycosyl compound
  • N-glycosyl compound
  • Halopyrimidine
  • Pyrimidone
  • Aryl fluoride
  • Aryl halide
  • Pyrimidine
  • Hydropyrimidine
  • Heteroaromatic compound
  • Tetrahydrofuran
  • Secondary alcohol
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidic acid derivative
  • Organopnictogen compound
  • Organohalogen compound
  • Organofluoride
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Alcohol
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point110-121°C
Boiling PointNot Available
Solubility26 mg/mL
LogP0.4
Predicted Properties
PropertyValueSource
Water Solubility0.25 g/LALOGPS
logP1.17ALOGPS
logP0.77ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)8.23ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area120.69 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity82.75 m³·mol⁻¹ChemAxon
Polarizability35.81 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ab9-9112000000-35a3e944454fc6eca103JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0079-9502500000-bb4d3c6463fb0a87a997JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0a4i-0109000000-c0c4de3c4233af3f34d4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0901000000-676f6925c6c255f4dd24JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0900000000-236cb917e50b215b9bd1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-1900000000-f06b7309e7a2ebfb3bdeJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0ufr-3900000000-6bb1981f61b4205a9991JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0kdi-6900000000-ac9a56401938b72ae4f1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0309000000-feac9f5163221adf2a7dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udj-0912000000-258b837e7c98d16aafbfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0900000000-db3e2d6a5526611d6a6eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0900000000-b792e6750d1eaccca7aaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0pb9-0609000000-cd05885e7f4f8d1853ecJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0090000000-8029f6bc09ef7062240eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-006x-0590000000-8cea6a9f156f58ccb593JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00e9-0920000000-e942daf2b25f1829bec1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0089-0900000000-2a5dcf8bb6ff7ae6d72fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-460a3e3f1f8b25687c86JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-0090000000-6105bf5c619fbe72100aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-af842efa254483370f53JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-1900000000-61c84595e7254f9493c9JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-2090000000-4b8cf489e15586dfdae8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-006x-5390000000-679252cae00158da4c5aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0096-9250000000-13f9259c8bd82a744463JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-006y-2792000000-3a1107d332a241bc2b9dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f6x-3691000000-15dcc8cfd9d6e268fa7eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0076-7950000000-99f8f0926e3b4607c61bJSpectraViewer
Toxicity Profile
Route of ExposureReadily absorbed through the GI tract (~70%)
Mechanism of ToxicityCapecitabine 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.
MetabolismMetabolized by thymidine phosphorylase to fluoruracil. Route of Elimination: Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug. Half Life: 45-60 minutes for capecitabine and its metabolites.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. May also be used in combination with docetaxel for the treatment of metastatic breast cancer in patients who have failed to respond to, or recurred or relasped during or following anthracycline-containing chemotherapy. Capecitabine is used alone as an adjuvant therapy following the complete resection of primary tumor in patients with stage III colon cancer when monotherapy with fluroprymidine is preferred. The use or capecitabine in combination regimens for advanced gastric cancer is currently being investigated.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01101
HMDB IDHMDB15233
PubChem Compound ID60953
ChEMBL IDCHEMBL1773
ChemSpider ID54916
KEGG IDC12650
UniProt IDNot Available
OMIM ID
ChEBI ID31348
BioCyc IDNot Available
CTD IDNot Available
Stitch IDCapecitabine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCapecitabine
References
Synthesis Reference

DrugSyn.org

MSDST3D3507.pdf
General References
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [15763604 ]
  2. Wagstaff AJ, Ibbotson T, Goa KL: Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63(2):217-36. [12515569 ]
  3. Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J: Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules. 2008 Aug 27;13(8):1897-922. [18794792 ]
  4. Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. [11585973 ]
  5. Milano G, Ferrero JM, Francois E: Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation. Br J Cancer. 2004 Aug 16;91(4):613-7. [15280932 ]
  6. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [11291832 ]
  7. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [15763604 ]
  2. Thomas DM, Zalcberg JR: 5-fluorouracil: a pharmacological paradigm in the use of cytotoxics. Clin Exp Pharmacol Physiol. 1998 Nov;25(11):887-95. [9807659 ]
  3. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. doi: 10.1007/s00018-008-8557-5. [18979208 ]
  4. Ghoshal K, Jacob ST: An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol. 1997 Jun 1;53(11):1569-75. [9264308 ]
  5. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [12724731 ]
  6. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. [15032669 ]
2. RNA
References
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [15763604 ]
  2. Thomas DM, Zalcberg JR: 5-fluorouracil: a pharmacological paradigm in the use of cytotoxics. Clin Exp Pharmacol Physiol. 1998 Nov;25(11):887-95. [9807659 ]
  3. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. doi: 10.1007/s00018-008-8557-5. [18979208 ]
  4. Ghoshal K, Jacob ST: An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol. 1997 Jun 1;53(11):1569-75. [9264308 ]
  5. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [12724731 ]
  6. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. [15032669 ]
General Function:
Protein homodimerization activity
Specific Function:
Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
Gene Name:
DPYD
Uniprot ID:
Q12882
Molecular Weight:
111400.32 Da
References
  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [11291832 ]
  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. [11587492 ]
  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. [12481438 ]
  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. [12527930 ]
  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. [12866042 ]
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
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. [15132128 ]
  2. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. [15134221 ]
  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. [15709193 ]
  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. [15866500 ]
  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. [16926630 ]