You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameCapecitabine
Accession NumberDB01101  (APRD00203)
TypeSmall Molecule
GroupsApproved, Investigational
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 fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.

Structure
Thumb
Synonyms
(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-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate
Pentyl 1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamate
Xeloda
External Identifiers
  • R340
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ach-capecitabinetablet500 mgoralAccord Healthcare Inc2014-09-19Not applicableCanada
Ach-capecitabinetablet150 mgoralAccord Healthcare Inc2014-09-19Not applicableCanada
Sandoz Capecitabinetablet500 mgoralSandoz Canada Incorporated2014-07-23Not applicableCanada
Sandoz Capecitabinetablet150 mgoralSandoz Canada Incorporated2014-07-23Not applicableCanada
Teva-capecitabinetablet500 mgoralTeva Canada Limited2013-08-19Not applicableCanada
Teva-capecitabinetablet150 mgoralTeva Canada Limited2013-08-19Not applicableCanada
Xelodatablet, film coated150 mg/1oralGenentech, Inc.1998-04-302016-04-23Us
Xelodatablet500 mgoralHoffmann La Roche Limited1998-09-10Not applicableCanada
Xelodatablet150 mgoralHoffmann La Roche Limited1998-09-10Not applicableCanada
Xelodatablet, film coated500 mg/1oralPhysicians Total Care, Inc.2005-06-282016-04-05Us
Xelodatablet, film coated150 mg/1oralPhysicians Total Care, Inc.2005-02-202016-04-05Us
Xelodatablet, film coated500 mg/1oralState of Florida DOH Central Pharmacy2009-07-012016-04-05Us
Xelodatablet, film coated500 mg/1oralGenentech, Inc.1998-04-302016-04-23Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-capecitabinetablet500 mgoralApotex IncNot applicableNot applicableCanada
Apo-capecitabinetablet150 mgoralApotex IncNot applicableNot applicableCanada
Capecitabinetablet, film coated150 mg/1oralAccord Healthcare Inc.2015-05-222016-04-05Us
Capecitabinetablet, film coated150 mg/1oralTeva Pharmaceuticals USA Inc2014-03-072016-04-23Us
Capecitabinetablet, film coated500 mg/1oralNorthstar Rx LLC2015-11-012016-04-05Us
Capecitabinetablet, film coated150 mg/1oralNorthstar Rx LLC2015-11-012016-04-05Us
Capecitabinetablet, film coated500 mg/1oralAmerican Health Packaging2015-10-012016-04-05Us
Capecitabinetablet, film coated500 mg/1oralMylan Pharmaceuticals Inc.2014-08-082016-04-23Us
Capecitabinetablet, film coated500 mg/1oralMylan Institutional Inc.2014-08-232016-04-05Us
Capecitabinetablet, film coated150 mg/1oralMylan Pharmaceuticals Inc.2014-08-082016-04-23Us
Capecitabinetablet, film coated500 mg/1oralAv Kare, Inc.2015-03-202016-04-05Us
Capecitabinetablet, film coated500 mg/1oralKAISER FOUNDATION HOSPITALS2015-12-022016-04-23Us
Capecitabinetablet, film coated150 mg/1oralAv Kare, Inc.2015-03-202016-04-05Us
Capecitabinetablet, film coated500 mg/1oralKAISER FOUNDATION HOSPITALS2014-05-142016-04-23Us
Capecitabinetablet, film coated500 mg/1oralAccord Healthcare Inc.2015-05-202016-04-05Us
Capecitabinetablet, film coated500 mg/1oralTeva Pharmaceuticals USA Inc2014-03-072016-04-23Us
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII6804DJ8Z9U
CAS number154361-50-9
WeightAverage: 359.3501
Monoisotopic: 359.149263656
Chemical FormulaC15H22FN3O6
InChI KeyInChIKey=GAGWJHPBXLXJQN-UORFTKCHSA-N
InChI
InChI=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
IUPAC Name
pentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate
SMILES
CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[[email protected]](C)[C@@H](O)[[email protected]]1O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as glycosylamines. These are compounds consisting of an amine with a beta-N-glycosidic bond to a carbohydrate, thus forming a cyclic hemiaminal ether bond (alpha-amino ether).
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassGlycosyl compounds
Direct ParentGlycosylamines
Alternative Parents
Substituents
  • N-glycosyl compound
  • Pyrimidone
  • Halopyrimidine
  • Aminopyrimidine
  • Imidolactam
  • Pyrimidine
  • Hydropyrimidine
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Oxolane
  • Secondary alcohol
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsCapecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).
Mechanism of actionCapecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. 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, therefore a deficiency of this compound can inhibit cell division. Secondly, 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 through the production of fraudulent RNA.
Related Articles
AbsorptionReadily absorbed through the GI tract (~70%)
Volume of distributionNot Available
Protein binding< 60% (mainly albumin)
Metabolism

Metabolized by thymidine phosphorylase to fluoruracil.

SubstrateEnzymesProduct
Capecitabine
5’-Deoxy-5-fluorouridineDetails
5’-Deoxy-5-fluorouridine
5-fluorouracilDetails
Route of eliminationCapecitabine 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 life45-60 minutes for capecitabine and its metabolites.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Capecitabine Metabolism PathwayDrug metabolismSMP00607
Capecitabine Action PathwayDrug actionSMP00469
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9513
Blood Brain Barrier+0.6064
Caco-2 permeable-0.7096
P-glycoprotein substrateSubstrate0.5106
P-glycoprotein inhibitor INon-inhibitor0.8234
P-glycoprotein inhibitor IINon-inhibitor0.7514
Renal organic cation transporterNon-inhibitor0.9654
CYP450 2C9 substrateNon-substrate0.7999
CYP450 2D6 substrateNon-substrate0.864
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.7523
CYP450 2C9 inhibitorNon-inhibitor0.7673
CYP450 2D6 inhibitorNon-inhibitor0.8612
CYP450 2C19 inhibitorNon-inhibitor0.6569
CYP450 3A4 inhibitorNon-inhibitor0.7404
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8484
Ames testNon AMES toxic0.6521
CarcinogenicityNon-carcinogens0.8754
BiodegradationNot ready biodegradable0.9964
Rat acute toxicity2.4690 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9759
hERG inhibition (predictor II)Non-inhibitor0.7124
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral150 mg
Tabletoral500 mg
Tablet, film coatedoral150 mg/1
Tablet, film coatedoral500 mg/1
Prices
Unit descriptionCostUnit
Xeloda 500 mg tablet28.97USD tablet
Xeloda 150 mg tablet8.69USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1327358 No1994-03-012011-03-01Canada
CA2103324 No1997-12-232013-11-17Canada
US4966891 No1994-01-132011-01-13Us
US5472949 No1993-12-142013-12-14Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point110-121 °CNot Available
water solubility26 mg/mLNot Available
logP0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.248 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity82.75 m3·mol-1ChemAxon
Polarizability35.81 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5472949
General References
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed: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. [PubMed: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. [PubMed:18794792 ]
  4. Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. [PubMed: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. [PubMed:15280932 ]
  6. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832 ]
External Links
ATC CodesL01BC06
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (133 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Capecitabine.
BosentanThe serum concentration of Bosentan can be increased when it is combined with Capecitabine.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Capecitabine.
CimetidineThe serum concentration of the active metabolites of Capecitabine can be increased when Capecitabine is used in combination with Cimetidine.
ClozapineThe risk or severity of adverse effects can be increased when Capecitabine is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Capecitabine.
DiclofenacThe serum concentration of Diclofenac can be increased when it is combined with Capecitabine.
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Capecitabine.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Capecitabine.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Capecitabine.
GimeracilThe serum concentration of the active metabolites of Capecitabine can be increased when Capecitabine is used in combination with Gimeracil.
LacosamideThe serum concentration of Lacosamide can be increased when it is combined with Capecitabine.
LeflunomideThe risk or severity of adverse effects can be increased when Capecitabine is combined with Leflunomide.
LeucovorinThe risk or severity of adverse effects can be increased when Leucovorin is combined with Capecitabine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Capecitabine.
MetronidazoleThe serum concentration of the active metabolites of Capecitabine can be increased when Capecitabine is used in combination with Metronidazole.
NatalizumabThe risk or severity of adverse effects can be increased when Capecitabine is combined with Natalizumab.
OspemifeneThe serum concentration of Ospemifene can be increased when it is combined with Capecitabine.
ParecoxibThe serum concentration of Parecoxib can be increased when it is combined with Capecitabine.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Capecitabine.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Capecitabine.
RamelteonThe serum concentration of Ramelteon can be increased when it is combined with Capecitabine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Capecitabine.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Capecitabine.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Capecitabine.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Capecitabine.
TofacitinibCapecitabine may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Capecitabine.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Capecitabine.
Food Interactions
  • Take 12 hours apart, within 30 minutes of the end of breakfast and dinner to reduce nausea.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:16926630 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
incorporation into and destabilization
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15032669 ]
3. RNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
incorporation into and destabilization
References
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15032669 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transferase activity, transferring pentosyl groups
Specific Function:
May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Gene Name:
TYMP
Uniprot ID:
P19971
Molecular Weight:
49954.965 Da
References
  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed: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. [PubMed: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. [PubMed:12481438 ]
  4. Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine]. Yakugaku Zasshi. 1999 Dec;119(12):881-97. [PubMed:10630095 ]
  5. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570 ]
  6. 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:12866042 ]
  7. Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B: Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45(4):291-7. [PubMed:10755317 ]
  8. 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:15132128 ]
  9. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. [PubMed:15134221 ]
  10. 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:16926630 ]
  11. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed:15763604 ]
  12. Ranieri G, Roccaro AM, Vacca A, Ribatti D: Thymidine phosphorylase (platelet-derived endothelial cell growth factor) as a target for capecitabine: from biology to the bedside. Recent Pat Anticancer Drug Discov. 2006 Jun;1(2):171-83. [PubMed:18221035 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Triglyceride lipase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity,...
Gene Name:
CES1
Uniprot ID:
P23141
Molecular Weight:
62520.62 Da
References
  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed: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. [PubMed:11587492 ]
  3. Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine]. Yakugaku Zasshi. 1999 Dec;119(12):881-97. [PubMed:10630095 ]
  4. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570 ]
  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:12866042 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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. 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:11587492 ]
  2. 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:12481438 ]
  3. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832 ]
  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:12527930 ]
  5. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570 ]
  6. 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:12866042 ]
  7. 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:15132128 ]
  8. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. [PubMed:15134221 ]
  9. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed:15763604 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Zinc ion binding
Specific Function:
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Gene Name:
CDA
Uniprot ID:
P32320
Molecular Weight:
16184.545 Da
References
  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed: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. [PubMed:11587492 ]
  3. Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine]. Yakugaku Zasshi. 1999 Dec;119(12):881-97. [PubMed:10630095 ]
  4. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570 ]
  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:12866042 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:22