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| Name | Capecitabine | ||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB01101 (APRD00203) | ||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||||||||
| 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. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Salts | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Brand mixtures | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 154361-50-9 | ||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 359.3501 Monoisotopic: 359.149263656 |
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| Chemical Formula | C15H22FN3O6 | ||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=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
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| 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
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| SMILES |
CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||||||||
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| 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. | ||||||||||||||||||||||||||||||||||||||||||
| 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. | ||||||||||||||||||||||||||||||||||||||||||
| 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. | ||||||||||||||||||||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Properties | |||||||||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| General Reference |
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (133 KB) | ||||||||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Targets |
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Pharmacological action: yes
Actions: inhibitor Organism class: human UniProt ID: P04818 ![]() Gene: TYMS ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. DNA Pharmacological action: yesActions: 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. Gene Sequence: FASTAReferences:
3. RNA Pharmacological action: yesActions: incorporation into and destabilization References:
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| Enzymes |
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Actions: substrate
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 UniProt ID: P19971![]() Gene: ECGF1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
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 UniProt ID: P23141![]() Gene: CES1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. Dihydropyrimidine dehydrogenase [NADP+] Actions: substrateInvolved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil UniProt ID: Q12882![]() Gene: DPYD ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
This enzyme scavenge exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis UniProt ID: P32320![]() Gene: CDA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
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, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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