10356-76-0 Usage
Description
2'-Deoxy-5-fluorocytidine, also known as 5-Fluoro-2'-deoxycytidine, is an antimetabolite consisting of a fluorinated pyrimidine analog with potential antineoplastic activity. It is a fine white powder that functions as a prodrug, which is converted by intracellular deaminases to the cytotoxic agent 5-Fluorouracil (5-FU). This conversion leads to the production of active metabolites that inhibit DNA and RNA synthesis, thereby disrupting cell division and growth.
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
Check Digit Verification of cas no
The CAS Registry Mumber 10356-76-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,0,3,5 and 6 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 10356-76:
(7*1)+(6*0)+(5*3)+(4*5)+(3*6)+(2*7)+(1*6)=80
80 % 10 = 0
So 10356-76-0 is a valid CAS Registry Number.
