Identification

Name
Capecitabine
Accession Number
DB01101
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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 359.3501
Monoisotopic: 359.149263656
Chemical Formula
C15H22FN3O6
Synonyms
  • (1-(5-Deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-carbamic acid pentyl ester
  • Capecitabin
  • Capecitabina
  • Capécitabine
  • Capecitabine
  • Capecitabinum
  • Pentyl [1-(5-deoxy-β-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate
  • pentyl 1-(5-deoxy-β-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamate
External IDs
  • R340
  • RO 09-1978/000
  • RO-09-1978/000

Pharmacology

Indication

For 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.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Capecitabine 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 action

Capecitabine 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.

TargetActionsOrganism
AThymidylate synthase
inhibitor
Humans
ADNA
incorporation into and destabilization
Humans
ARNA
incorporation into and destabilization
Humans
Absorption

Readily absorbed through the GI tract (~70%)

Volume of distribution
Not Available
Protein binding

< 60% (mainly albumin)

Metabolism

Metabolized by thymidine phosphorylase to fluoruracil.

Hover over products below to view reaction partners

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.

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Capecitabine Action PathwayDrug action
Capecitabine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*2A(A;A) / (A;G)G > AADR Directly StudiedThe presence of this genotype in DPYD is associated with an increased risk of drug-related toxicity from capecitabine therapy.Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*13(C;C) / (A;C)A > CADR Directly StudiedThe presence of this genotype in DPYD is associated with an increased risk of drug-related toxicity from capecitabine therapy.Details
Dihydropyrimidine dehydrogenase [NADP(+)]---(A;A) / (A;T)T > AADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from capecitabine therapy.Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*4(G;G) / (A:G)G > AADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from capecitabine therapy.Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*5(G;G) / (A;G)A > GADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from capecitabine therapy.Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*6(A;A) / (A;G)G > AADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from capecitabine therapy.Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*9A(C;C) / (C;T)T > CADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from capecitabine therapy.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Capecitabine which could result in a higher serum level.
AbataceptThe metabolism of Abatacept can be increased when combined with Capecitabine.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Capecitabine.
AbirateroneThe metabolism of Capecitabine can be decreased when combined with Abiraterone.
AcarboseAcarbose may decrease the excretion rate of Capecitabine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Capecitabine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Capecitabine which could result in a higher serum level.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Capecitabine.
AcetaminophenAcetaminophen may decrease the excretion rate of Capecitabine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Capecitabine which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with food. Take within 30 minutes of the end of breakfast and dinner.

Products

Active Moieties
NameKindUNIICASInChI Key
FluorouracilprodrugU3P01618RT51-21-8GHASVSINZRGABV-UHFFFAOYSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Capecitabine Tablets, 150 mgTablet150 mg/1OralProdigy Innovation, LLC.2019-04-22Not applicableUs
Capecitabine Tablets, 500 mgTablet500 mg/1OralProdigy Innovation, LLC.2019-04-22Not applicableUs
XelodaTablet, film coated150 mg/1OralPhysicians Total Care, Inc.2005-02-20Not applicableUs
XelodaTablet150 mgOralHoffmann La Roche1998-09-10Not applicableCanada
XelodaTablet, film coated500 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs53808 041120180907 15195 kwmhpm
XelodaTablet, film coated500 mg/1OralGenentech, Inc.1998-04-30Not applicableUs0004 110120180810 16125 cbr16j
XelodaTablet, film coated500 mg/1OralPhysicians Total Care, Inc.2005-06-28Not applicableUs00004 1101 50 nlmimage10 3e3d1f08
XelodaTablet, film coated150 mg/1OralGenentech, Inc.1998-04-30Not applicableUs
XelodaTablet500 mgOralHoffmann La Roche1998-09-10Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-capecitabineTabletOralAccord Healthcare Inc2014-09-19Not applicableCanada
Ach-capecitabineTabletOralAccord Healthcare Inc2014-09-19Not applicableCanada
Apo-capecitabineTabletOralApotex CorporationNot applicableNot applicableCanada
Apo-capecitabineTabletOralApotex CorporationNot applicableNot applicableCanada
CapecitabineTablet, film coated500 mg/1OralNorthstar RxLLC2015-11-01Not applicableUs
CapecitabineTablet, film coated150 mg/1OralTeva Pharmaceuticals USA, Inc.2014-03-07Not applicableUs0093 747320180907 15195 1qipe8g
CapecitabineTablet, film coated500 mg/1OralAccord Healthcare Inc.2015-05-20Not applicableUs
CapecitabineTablet, film coated150 mg/1OralMsn Laboratories Private Limited2018-07-02Not applicableUs
CapecitabineTablet, film coated500 mg/1OralSun Pharmaceutical Industries, Inc.2019-09-01Not applicableUs
CapecitabineTablet, film coated150 mg/1OralAscend Laboratories, LLC2017-11-25Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01BC06 — Capecitabine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
5'-deoxyribonucleosides
Sub Class
Not Available
Direct Parent
5'-deoxyribonucleosides
Alternative Parents
Glycosylamines / Pyrimidones / Halopyrimidines / Aryl fluorides / Hydropyrimidines / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / 1,2-diols / Propargyl-type 1,3-dipolar organic compounds
show 8 more
Substituents
1,2-diol / 5'-deoxyribonucleoside / Alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Carboximidic acid derivative / Glycosyl compound / Halopyrimidine
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, carbamate ester, cytidines (CHEBI:31348)

Chemical Identifiers

UNII
6804DJ8Z9U
CAS number
154361-50-9
InChI Key
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[C@H](C)[C@@H](O)[C@H]1O

References

Synthesis Reference
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]
Human Metabolome Database
HMDB0015233
KEGG Drug
D01223
KEGG Compound
C12650
PubChem Compound
60953
PubChem Substance
46508686
ChemSpider
54916
RxNav
194000
ChEBI
31348
ChEMBL
CHEMBL1773
ZINC
ZINC000003806413
Therapeutic Targets Database
DAP000761
PharmGKB
PA448771
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Capecitabine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (133 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Approved for MarketingNot AvailableNeoplasms, Breast1
4CompletedBasic ScienceAdenocarcinoma of the Pancreas1
4CompletedDiagnosticBreast Cancer / Colorectal Cancers1
4CompletedOtherHER2/Neu-negative Carcinoma of Breast / Hormone Receptor Positive Malignant Neoplasm of Breast / Recurrent Breast Cancer1
4CompletedTreatmentBreast Cancer2
4CompletedTreatmentColorectal Cancers5
4CompletedTreatmentColorectal Cancers / Neoplasms, Colorectal1
4CompletedTreatmentUpper Gastrointestinal Tumours1
4Not Yet RecruitingBasic ScienceBreast Cancer / Colorectal Cancers1
4RecruitingTreatmentHer-2 Positive Gastric Cancer / Liver Metastasis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Dept Health Central Pharmacy
  • F Hoffmann-La Roche Ltd.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
TabletOral150 mg/1
TabletOral500 mg/1
Tablet, film coatedOral150 mg
Tablet, film coatedOral300 mg
Tablet, film coatedOral500 mg
TabletOral
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)Region
US5472949No1995-12-052013-12-14Us
US4966891No1990-10-302011-01-13Us
CA2103324No1997-12-232013-11-17Canada
CA1327358No1994-03-012011-03-01Canada
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)110-121 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0109000000-c0c4de3c4233af3f34d4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0901000000-676f6925c6c255f4dd24
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-236cb917e50b215b9bd1
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-1900000000-f06b7309e7a2ebfb3bde
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0ufr-3900000000-6bb1981f61b4205a9991
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0kdi-6900000000-ac9a56401938b72ae4f1
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0309000000-feac9f5163221adf2a7d
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udj-0912000000-258b837e7c98d16aafbf
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udi-0900000000-db3e2d6a5526611d6a6e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udi-0900000000-b792e6750d1eaccca7aa
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0pb9-0609000000-cd05885e7f4f8d1853ec
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0090000000-8029f6bc09ef7062240e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-006x-0590000000-8cea6a9f156f58ccb593
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00e9-0920000000-e942daf2b25f1829bec1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0089-0900000000-2a5dcf8bb6ff7ae6d72f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-460a3e3f1f8b25687c86
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0090000000-6105bf5c619fbe72100a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-af842efa254483370f53
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1900000000-61c84595e7254f9493c9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0900000000-25912e0277815dec7dfc
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0900000000-f992985efa9f7da2dbba
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0090000000-6ec0fa0ed4f779ff959a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0090000000-3be9f054ad6d351dfcda
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-007o-0960000000-eeaa7c678c405b7f7e1f

Targets

Kind
Protein
Organism
Humans
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
Uniprot Name
Thymidylate synthase
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]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Incorporation into and destabilization
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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]
Kind
Nucleotide
Organism
Humans
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
Humans
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 v...
Gene Name
TYMP
Uniprot ID
P19971
Uniprot Name
Thymidine phosphorylase
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
Humans
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 acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
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
Humans
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
Uniprot Name
Dihydropyrimidine dehydrogenase [NADP(+)]
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
Humans
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
Uniprot Name
Cytidine deaminase
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
Humans
Pharmacological action
Unknown
Actions
Substrate
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Janney LM, Waterbury NV: Capecitabine-warfarin interaction. Ann Pharmacother. 2005 Sep;39(9):1546-51. doi: 10.1345/aph.1G153. Epub 2005 Jul 12. [PubMed:16014372]
  2. Seredina TA, Goreva OB, Talaban VO, Grishanova AY, Lyakhovich VV: Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients. BMC Med Genet. 2012 Jun 15;13:45. doi: 10.1186/1471-2350-13-45. [PubMed:22702493]
  3. Capecitabine FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on August 05, 2020 23:35

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