化合物信息

ID:972

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

质子受体

质子供体

LogD (pH = 5.5)

0.76731384

LogD (pH = 7.4)

0.71495193

Log P

0.76803607

摩尔折射率

82.746

极化性

32.438602

极化表面积

120.69

可自由旋转的化学键

里宾斯基五规则

true

Log P

1.17

LOG S

-3.16

溶解度

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

美国药典/FDA物质标识码

疏水性(logP)

0.4

溶解度

26 mg/mL

DMSO

纯度

95+%

成盐信息

Free Base

TSCA收录

false

MSDS下载

下载链接

保存注意事项

IRRITANT

保存条件

-20°C

• 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.

名称和标识

别名

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标准名

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

商标名

Xeloda

IUPAC传统名

capecitabine CAPE

数据登录号

CAS号

PubChem SID

PubChem CID

ATC码

CHEBI ID

CHEMBL

维基百科标题

Medline Plus

美国药典/FDA物质标识码

DrugBank ID

KEGG ID

Chemspider ID

MDL号

参考文献

PubChem文献

数据源提供

• 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.

生物活性

PubChem BioAssay

描述信息

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.