| Identification | More | [Name]
2'-DEOXY-5-FLUOROCYTIDINE | [CAS]
10356-76-0 | [Synonyms]
2'-DEOXY-5-FLUOROCYTIDINE
5-FLUORO-2'-DEOXYCYTIDINE
2’-deoxy-5-fluoro-cytidin
5-fluor-desoxycytidin
5-fluorodeoxycytidine | [Molecular Formula]
C9H12FN3O4 | [MDL Number]
MFCD00077348 | [Molecular Weight]
245.21 | [MOL File]
10356-76-0.mol |
| Chemical Properties | Back Directory | [Description]
5-Fluoro-2-Deoxycytidine is an antimetabolite consisting of a fluorinated pyrimidine analog with potential antineoplastic activity. As a prodrug, 5-fluoro-2-deoxycytidine is converted by intracellular deaminases to the cytotoxic agent 5-Fluorouracil (5-FU). 5-FU is subsequently metabolized to active metabolites including 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP binds to and inhibits thymidylate synthase, thereby reducing the production of thymidine monophosphate, which leads to depletion of thymidine triphosphate. This inhibits DNA synthesis and cell division. FUTP competes with uridine triphosphate for incorporation into the RNA strand thus leading to an inhibition of RNA and protein synthesis. Other fluorouracil metabolites also get incorporated into both DNA and RNA, thereby further hampering cellular growth. | [Melting point ]
196 °C | [Boiling point ]
465℃ | [density ]
1.82 | [refractive index ]
70 ° (C=1, H2O) | [Fp ]
235℃ | [storage temp. ]
Keep in dark place,Inert atmosphere,2-8°C | [solubility ]
DMSO: >20mg/mL | [form ]
A crystalline solid | [pka]
14.03±0.60(Predicted) | [color ]
white to off-white | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. | [Uses]
5-fluoro-2'-deoxycytidine has been used in trials studying the treatment of Neoplasms, Lung Neoplasms, Breast Neoplasms, Head and Neck Neoplasms, and Urinary Bladder Neoplasms, among others. | [CAS DataBase Reference]
10356-76-0(CAS DataBase Reference) | [EPA Substance Registry System]
5-Fluoro-2'-deoxycytidine (10356-76-0) |
| Hazard Information | Back Directory | [General Description]
Fine white powder. | [Air & Water Reactions]
This chemical is probably light and air sensitive. | [Health Hazard]
ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits toxic fumes of fluoride ion and NOx. | [Fire Hazard]
Flash point data for this chemical are not available. 5-FLUORO-2'-DEOXYCYTIDINE is probably combustible. | [Pharmacology]
5-Fluoro-2'-deoxycytidine (FdCyd), a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, coadministration with tetrahydrouridine (THU), an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the AUC of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into DNA and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
Primary objective:
-Determine progression-free survival (PFS) and/or the response rate (CR + PR) of FdCyd administered 5 days per week for 2 weeks, in 28-day cycles, by intravenous infusion over 3 hours along with THU in patients with breast cancer, head and neck cancer, non-small cell lung cancer, and urothelial transitional cell carcinoma.
Exploratory objectives:
Evaluate whether treatment with FdCyd and THU alters DNA methylation patterns in tumor biopsy samples before and during treatment by LINE-1 analysis.
Evaluate the safety and tolerability of FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days per week for 2 weeks, in 28-day cycles, by intravenous infusion over 3 hours.
Measure changes in the number of CTCs following treatment with FdCyd plus THU. | [Clinical Use]
A DNA methyltransferase inhibitor currently in clinical trials for breast cancer and other solid tumors. Like 5’-Azacytidine and decitabine, 2’-Deoxy-5-fluorocytidine is a pyrimidine analog that integrates into chromatin to inhibit DNA methylation. It blocks proliferation in colon cancer-derived HCT116 cells by activating DNA response pathways. It inhibits various strains of pathogenic avian influenza viruses in vitro and in vivo. | [storage]
4°C, protect from light | [References]
1) Ren?et al. (2011),?DNA hypermethylation as a chemotherapy target; Cell Signal,?23?1082
2) Gowher?et al. (2004),?Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy; Cancer Biol. Ther.,?3?1062
3) Zhao?et al. (2002),?Inhibition of cancer cell proliferation by 5-fluoro-2′-deoxycytidine, a DNA methylation inhibitor, through activation of DNA damage response pathway; Springerplus,?1?65
4) Kumaki?et al. (2001),?In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections; Antiviral Res.,?92?329 |
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