10356-76-0

Basic information

• Product Name: 2'-DEOXY-5-FLUOROCYTIDINE
• Synonyms: 2'-DEOXY-5-FLUOROCYTIDINE;5-FLUORO-2'-DEOXYCYTIDINE;2’-deoxy-5-fluoro-cytidin;5-fluor-desoxycytidin;5-fluorodeoxycytidine;NSC 48006;Ro 5-1090;5--F-dC
• CAS NO: 10356-76-0
• Molecular Formula: C₉H₁₂FN₃O₄
• Molecular Weight: 245.21
• Product Categories: Biochemistry;Nucleosides and their analogs;Nucleosides, Nucleotides & Related Reagents
• Mol File: 10356-76-0.mol

Chemical Properties

• Melting Point: 196 °C
• Boiling Point: 465℃
• Flash Point: 235℃
• Appearance: white to off-white/
• Density: 1.82
• Refractive Index: 70 ° (C=1, H2O)
• Storage Temp.: room temp
• Solubility: DMSO: >20mg/mL
• PKA: 14.03±0.60(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• CAS DataBase Reference: 2'-DEOXY-5-FLUOROCYTIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2'-DEOXY-5-FLUOROCYTIDINE(10356-76-0)
• EPA Substance Registry System: 2'-DEOXY-5-FLUOROCYTIDINE(10356-76-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: HA3850000
• Hazardous Substances Data: 10356-76-0(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
2'-Deoxy-5-fluorocytidine is used as a mechanism-based DNMT inhibitor for the treatment of various types of neoplasms, including lung, breast, head and neck, and urinary bladder neoplasms. It modulates the activity of DNA methyltransferases, which are enzymes involved in the regulation of gene expression and are often dysregulated in cancer cells. By inhibiting these enzymes, 2'-deoxy-5-fluorocytidine can help restore normal gene expression patterns and potentially halt tumor growth.
Used in Clinical Trials:
2'-Deoxy-5-fluorocytidine has been utilized in clinical trials studying the treatment of various types of cancer. These trials aim to evaluate the safety, efficacy, and optimal dosing regimens for this compound in different patient populations and cancer types.
Used in Drug Development:
As a prodrug, 2'-deoxy-5-fluorocytidine is used in the development of new antineoplastic agents. Its conversion to 5-FU and subsequent metabolites provides a basis for the design of novel drugs that can target specific enzymes or pathways involved in cancer cell growth and survival.
Used in Research:
2'-Deoxy-5-fluorocytidine is also used as a research tool to study the mechanisms of action of various antineoplastic agents and to investigate the role of DNA methylation in cancer development and progression. This knowledge can help researchers develop more targeted and effective cancer therapies.

Air & Water Reactions

2'-DEOXY-5-FLUOROCYTIDINE is probably light and air sensitive.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition 2'-DEOXY-5-FLUOROCYTIDINE emits toxic fumes of fluoride ion and NOx.

Fire Hazard

Flash point data for 2'-DEOXY-5-FLUOROCYTIDINE are not available. 2'-DEOXY-5-FLUOROCYTIDINE 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.

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

Upstream product

• 78948-09-1 acetyl hypofluorite 
• 951-77-9 deoxycytidine 
• 92574-68-0 1-(3,5-di-O-benzoyl-2-deoxy-β-D-ribofuranosyl)-5-fluoro-N₄-p-toluoylcytosine 
• 161179-94-8 5-fluoro-4-(1,2,4-triazol-1-yl)-1-(3,5-di-O-acetyl-2-deoxy-β-D-ribofuranosyl)-pyrimidine-2(1H)-one 
• 110522-47-9 1-(2'-deoxy-3',5'-tri-O-acetyl-β-D-ribofuranosyl)-5-fluorouracil 
• 50-91-9 5-Fluoro-2'-deoxyuridine 
• 51255-12-0 1-O-acetyl-3,5-di-O-benzoyl-2-deoxy-D-ribofuranose 

Downstream Products

• 143774-47-4 5-fluoro-5'-(4,4'-dimethoxytrityl)-2'-deoxycytidine 
• 143774-48-5 5-fluoro-5'-(dimethoxytrityl)-2'-deoxycytid-3'-yl 2-cyanoethyl N,N-diisopropylphosphoramidite 

Relevant articles and documents

Reaction of Acetyl Hypofluorite with Pyrimidines. Part 3. Synthesis, Stereochemistry, and Properties of 5-Fluoro-5,6-dihydropyrimidine Nucleosides

The reaction of acetyl hypofluorite (AcOF) with unprotected uracil and cytosine nucleosides in acetic acid or water has been studied using (18)F as a tracer.For the nucleosides in general two cis-diastereoisomers of both the 6-acetoxy-5-fluoro and 5-fluoro-6-hydroxy adducts were obtained, (1)H n.m.r. analysis of which showed that they all possessed the anti-conformation.The 6-acetoxy-5-fluoroadducts in the uracil nucleosides showed a remarkable stability and appeared to be interesting versatile compounds.They could be converted into their hitherto unknown corresponding 5-fluoro-6-hydroxy-O6,5'-anhydrocyclouracil nucleosides.For the cytosine nucleosides the 6-acetoxy-5-fluoro adducts were not observed, while the other cytosine adducts were found to rapidly deaminate at C-4 in water yielding the corresponding uracil analogues.Interestingly, even within a pair of diastereoisomers different deamination rates were observed.

2,2'-Anhydro-β-D-arabinofuranosyl-5-fluorocytosine

A novel derivative of 1-β-D-arabinofuranose namely the 5-fluorocytosine derivative has been prepared and found to have excellent activity against mouse leukemia.