Capecitabine
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
Structure for Capecitabine (DB01101)
- 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
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- 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
- Duke's C Colon cancer
- Esophageal Cancers
- Hepatobiliary Cancers
- Malignant Neoplasm of Stomach
- Metastatic Breast Cancer
- Metastatic Colorectal Carcinoma
- Pancreatic Cancer Metastatic
- Refractory Fallopian Tube Carcinoma
- Metastatic pancreatic endocrine carcinoma
- Refractory Ovarian cancer
- Refractory peritoneal cancer
- Refractory, metastatic Colorectal carcinoma
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- 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.
Target Actions Organism AThymidylate synthase inhibitorHumans ADNA incorporation into and destabilizationHumans ARNA incorporation into and destabilizationHumans - 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
Reduce medical errorsand improve treatment outcomes with our comprehensive & structured data on drug adverse effects.Reduce medical errors & improve treatment outcomes with our adverse effects data- Toxicity
- Not Available
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Capecitabine Action Pathway Drug action Capecitabine Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Dihydropyrimidine dehydrogenase [NADP(+)] DPYD*2A (A;A) / (A;G) G > A ADR Directly Studied The 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 > C ADR Directly Studied The 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 > A ADR Directly Studied The 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 > A ADR Directly Studied The 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 > G ADR Directly Studied The 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 > A ADR Directly Studied The 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 > C ADR Directly Studied The 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Capecitabine which could result in a higher serum level. Abatacept The metabolism of Abatacept can be increased when combined with Capecitabine. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Capecitabine. Abiraterone The metabolism of Capecitabine can be decreased when combined with Abiraterone. Aceclofenac Aceclofenac may decrease the excretion rate of Capecitabine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Capecitabine which could result in a higher serum level. Acenocoumarol Acenocoumarol may increase the anticoagulant activities of Capecitabine. Acetaminophen Acetaminophen may decrease the excretion rate of Capecitabine which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Capecitabine which could result in a lower serum level and potentially a reduction in efficacy. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Capecitabine. 
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- Take with food. Take within 30 minutes of the end of breakfast and dinner.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Active Moieties
Name Kind UNII CAS InChI Key Fluorouracil prodrug U3P01618RT 51-21-8 GHASVSINZRGABV-UHFFFAOYSA-N - Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Capecitabine Accord Tablet, film coated 300 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU 
Capecitabine Accord Tablet, film coated 500 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 150 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 300 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 150 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 300 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 500 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 500 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 150 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Capecitabine Accord Tablet, film coated 500 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-capecitabine Tablet Oral Accord Healthcare Inc 2014-09-19 Not applicable Canada 
Ach-capecitabine Tablet Oral Accord Healthcare Inc 2014-09-19 Not applicable Canada Apo-capecitabine Tablet Oral Apotex Corporation Not applicable Not applicable Canada Apo-capecitabine Tablet Oral Apotex Corporation Not applicable Not applicable Canada Capecitabine Tablet, film coated 500 mg/1 Oral Novadoz Pharmaceuticals Llc 2018-07-21 Not applicable US 
Capecitabine Tablet, film coated 500 mg/1 Oral Mylan Pharmaceuticals Inc. 2014-08-08 Not applicable US Capecitabine Tablet 500 mg/1 Oral Aurobindo Pharma Limited 2018-04-17 Not applicable US Capecitabine Tablet, film coated 500 mg/1 Oral Shilpa Medicare Limited 2016-12-31 Not applicable US Capecitabine Tablet 500 mg/1 Oral KAISER FOUNDATION HOSPITALS 2017-09-01 2018-02-28 US Capecitabine Tablet, film coated 150 mg/1 Oral Ascend Laboratories, LLC 2017-11-25 Not applicable US
Categories
- ATC Codes
- L01BC06 — Capecitabine
- Drug Categories
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Carbohydrates
- Cardiotoxic antineoplastic agents
- Cytidine Deaminase Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strong)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Deoxycytidine
- Deoxyribonucleosides
- Drugs that are Mainly Renally Excreted
- Fluoropyrimidines
- Fluorouracil and prodrugs
- Glycosides
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Noxae
- Nucleic Acid Synthesis Inhibitors
- Nucleic Acids, Nucleotides, and Nucleosides
- Nucleoside Metabolic Inhibitor
- Nucleosides
- Pyrimidine Analogues
- Pyrimidine Nucleosides
- Pyrimidines
- Pyrimidinones
- Ribonucleosides
- Toxic Actions
- 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
- Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed:15763604]
- 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]
- 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]
- Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. [PubMed:11585973]
- 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]
- de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832]
- External Links
- Human Metabolome Database
- HMDB0015233
- KEGG Drug
- D01223
- KEGG Compound
- C12650
- PubChem Compound
- 60953
- PubChem Substance
- 46508686
- ChemSpider
- 54916
- 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
Phase Status Purpose Conditions Count 4 Completed Basic Science Adenocarcinoma of the Pancreas 1 4 Completed Diagnostic Breast Cancer / Colorectal Cancers 1 4 Completed Other HER2/Neu-negative Carcinoma of Breast / Hormone Receptor Positive Malignant Neoplasm of Breast / Recurrent Breast Cancer 1 4 Completed Treatment Breast Cancer 2 4 Completed Treatment Colorectal Cancers 5 4 Completed Treatment Neoplasms, Colorectal 1 4 Completed Treatment Upper Gastrointestinal Tumours 1 4 Recruiting Treatment Metastatic Breast Cancer 1 4 Recruiting Treatment Pancreatic Ductal Adenocarcinoma 1 4 Terminated Basic Science Adenocarcinoma of the Stomach 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Dept Health Central Pharmacy
- F Hoffmann-La Roche Ltd.
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Tablet, film coated Oral Tablet Oral 150 mg/1 Tablet Oral 500 mg/1 Tablet, film coated Oral 150 mg Tablet, film coated Oral 300 mg Tablet, film coated Oral 500 mg Tablet, coated Oral 500 mg Tablet, delayed release Oral 500 mg Tablet Oral Tablet Oral 150 mg Tablet Oral 500 mg Tablet, film coated Oral 150 mg/1 Tablet, film coated Oral 500 mg/1 Tablet, coated Oral 150 mg Tablet, coated Oral - Prices
Unit description Cost Unit Xeloda 500 mg tablet 28.97USD tablet Xeloda 150 mg tablet 8.69USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5472949 No 1995-12-05 2013-12-14 US US4966891 No 1990-10-30 2011-01-13 US CA2103324 No 1997-12-23 2013-11-17 Canada CA1327358 No 1994-03-01 2011-03-01 Canada
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 110-121 °C Not Available water solubility 26 mg/mL Not Available logP 0.4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.248 mg/mL ALOGPS logP 1.17 ALOGPS logP 0.77 ChemAxon logS -3.2 ALOGPS pKa (Strongest Acidic) 8.23 ChemAxon pKa (Strongest Basic) -3.6 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 120.69 Å2 ChemAxon Rotatable Bond Count 7 ChemAxon Refractivity 82.75 m3·mol-1 ChemAxon Polarizability 35.81 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9513 Blood Brain Barrier + 0.6064 Caco-2 permeable - 0.7096 P-glycoprotein substrate Substrate 0.5106 P-glycoprotein inhibitor I Non-inhibitor 0.8234 P-glycoprotein inhibitor II Non-inhibitor 0.7514 Renal organic cation transporter Non-inhibitor 0.9654 CYP450 2C9 substrate Non-substrate 0.7999 CYP450 2D6 substrate Non-substrate 0.864 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Non-inhibitor 0.7523 CYP450 2C9 inhibitor Non-inhibitor 0.7673 CYP450 2D6 inhibitor Non-inhibitor 0.8612 CYP450 2C19 inhibitor Non-inhibitor 0.6569 CYP450 3A4 inhibitor Non-inhibitor 0.7404 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8484 Ames test Non AMES toxic 0.6521 Carcinogenicity Non-carcinogens 0.8754 Biodegradation Not ready biodegradable 0.9964 Rat acute toxicity 2.4690 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9759 hERG inhibition (predictor II) Non-inhibitor 0.7124
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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with our fully connected ADMET & drug target dataset.
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- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Yes
Incorporation into and destabilization
References
- Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed:15763604]
- 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]
- 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]
- 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]
- 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]
- 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]
Yes
Incorporation into and destabilization
References
- Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed:15763604]
- 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]
- 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]
- 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]
- 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]
- 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
- de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832]
- 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]
- 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]
- Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine]. Yakugaku Zasshi. 1999 Dec;119(12):881-97. [PubMed:10630095]
- Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570]
- 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]
- 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]
- 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]
- 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]
- 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]
- Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [PubMed:15763604]
- 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
- de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832]
- 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]
- Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine]. Yakugaku Zasshi. 1999 Dec;119(12):881-97. [PubMed:10630095]
- Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570]
- 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
- 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]
- 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]
- de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832]
- 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]
- Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570]
- 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]
- 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]
- 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]
- 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
- de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [PubMed:11291832]
- 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]
- Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine]. Yakugaku Zasshi. 1999 Dec;119(12):881-97. [PubMed:10630095]
- Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. [PubMed:11081570]
- 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
- SubstrateInhibitor
- 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
- 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]
- 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]
- Capecitabine FDA label [File]
Drug created on June 13, 2005 13:24 / Updated on February 24, 2021 19:34