CAS 154361-50-9|Capecitabine|Xeloda|R340|capecitabine|capecitabine|pentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate|Capecitabine(Xelod...

C₁₅H₂₂FN₃O₆

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

GAGWJHPBXLXJQN-UORFTKCHSA-N

CCCCCOC(=O)Nc1nc(=O)n(cc1F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)C

Fc1cn([C@@H]2O[C@@H]([C@@H](O)[C@H]2O)C)c(=O)nc1NC(=O)OCCCCC

Acid pKa

8.226098

H Acceptors

H Donor

LogD (pH = 5.5)

0.76731384

LogD (pH = 7.4)

0.71495193

Log P

0.76803607

Molar Refractivity

82.746

Polarizability

32.438602

Polar Surface Area

120.69

Rotatable Bonds

Lipinski's Rule of Five

true

Log P

1.17

LOG S

-3.16

Solubility (Water)

2.48e-01 g/l

CapecitabineR340capecitabinePentyl (1-((2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamateXelodaCapecitabine(Xeloda)

pentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate

IUPAC Traditional name

Unique Ingredient Identifier

Solubility

26 mg/mL

DMSO

Hydrophobicity(logP)

0.4

MSDS Link

Download link

TSCA Listed

false

Storage Warning

IRRITANT

Storage Condition

-20°C

Purity

95+%

Salt Data

Free Base

Pharmacology Properties

Click here to submit data

• 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

• Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed

• Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. Pubmed

• 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

• 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

• de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed

• Ciccolini J, et al. Mol Cancer Ther. 2002, 1(11), 923-927.

• Zhou J, et al. Clin Cancer Res. 2003, 9(16), 6030-6037.

• Ishikawa T, et al. Biochem Pharmacol. 1998, 55(7), 1091-1097.

Names and Identifiers

Synonyms

CapecitabineR340capecitabinePentyl (1-((2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamateXelodaCapecitabine(Xeloda)

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

Brand Name

Xeloda

IUPAC Traditional name

capecitabine CAPE

Registration numbers

PubChem SID

CAS Number

PubChem CID

ATC CODE

Wikipedia Title

CHEBI ID

CHEMBL

Medline Plus

Unique Ingredient Identifier

Chemspider ID

DrugBank ID

KEGG ID

MDL Number

References

PubChem Literature

From Data Sources

• Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed

• Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. Pubmed

• 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

• de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed

• Ciccolini J, et al. Mol Cancer Ther. 2002, 1(11), 923-927.

• Zhou J, et al. Clin Cancer Res. 2003, 9(16), 6030-6037.

• Ishikawa T, et al. Biochem Pharmacol. 1998, 55(7), 1091-1097.

Bioactivity

PubChem BioAssay

Molecule Details

DrugBank

DB01101

Drug Groups

approved; 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.

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.

Pharmacology

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).

Affected Organisms

Humans and other mammals

Biotransformation

Metabolized by thymidine phosphorylase to fluoruracil.

Absorption

Readily absorbed through the GI tract (~70%)

Half Life

45-60 minutes for capecitabine and its metabolites.

Protein Binding

< 60% (mainly albumin)

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.

References

• Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. [Pubmed]

• 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]

• Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. [Pubmed]

• de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1156

Research Area

Description

Glioma,Oesophageal cancer, Colorectal cancer

Biological Activity

Description

Capecitabine is a tumor-selective fluoropyrimidine carbamate which achieves higher intratumoral 5-FU level with lower toxicity than 5-FU.

Targets

IC₅₀

In Vitro

Both LS174T WT and LS174T-c2 cells show significantly greater sensitivity to Capecitabine when cultivated in the same plates as HepG2 hepatoma with IC50 values of 890 and 630 μM in LS174T WT alone and cultivated with HepG2, respectively. In addition, for the LS174T-C2 subline, the IC50 falls from 330 ± 4 down to 89 ± 6 μm when cultivated in the same plates as hepatoma cells. Furthermore, Capecitabine induces apoptosis in a Fas-dependent manner, and shows a 7-fold higher cytotoxicity and markedly stronger apoptotic potential in thymidine phosphorylase (TP)-transfected LS174T-c2 cells. ^[1]

In Vivo

In the human cancer xenograft models studied, Capecitabine is more effective in a wider dose range and has a broader spectrum of antitumor activity than 5-FU, UFT or its intermediate metabolite 5'-DFUR, which can be correlated with tumor dThdPase levels. ^[2] Capecitabine inhibits tumor growth and metastatic recurrence after resection of human hepatocellular carcinoma (HCC) in highly metastatic nude mice model which is attributed to the high expression of platelet-derived endothelial cell growth factor in tumors. ^[3]

Clinical Trials

Capecitabine is currently under investigation in Phase II clinical trials in patients with Breast Cancer Metastasis.

Features

Capecitabine is a tumor-selective fluoropyrimidine carbamate.

Protocol

Kinase Assay ^[]

Cell Assay ^[1]

Cell Lines

HepG2, LS174T WT and LS174T-c2 cells

Concentrations

~1 mM

Incubation Time

72 hours

Methods

HepG2 and either LS174T WT or LS174T-c2 cells are seeded, respectively, in the top and bottom chambers of 8-well strip membranes in 96-well plates. The exponentially growing cells are exposed to increasing concentrations of capecitabine. The medium is supplemented with 750 ng/mL ZB4 MoAB or 100 ng/mL BR17 MoAB when the latter are used in the experiments. After 72 hours of continuous exposure, LS174T viability is assessed using the classic colorimetric MTT test.