Gemcitabine Impurity C (EP) - CAS 114248-23-6
Catalog number: 114248-23-6
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Gemcitabine Impurity C is a metabolite of Gemcitabine in human plasma.
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2’,2’-Difluoro-2’-deoxyuridine; 2’-Deoxy-2’,2’-difluorouridine; 2’,2’-Difluorodeoxyuridine
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1.Inhibition of thymidylate synthase by 2',2'-difluoro-2'-deoxycytidine (Gemcitabine) and its metabolite 2',2'-difluoro-2'-deoxyuridine.
Honeywell RJ1, Ruiz van Haperen VW2, Veerman G3, Smid K1, Peters GJ4. Int J Biochem Cell Biol. 2015 Mar;60:73-81. doi: 10.1016/j.biocel.2014.12.010. Epub 2015 Jan 3.
2',2'-Difluoro-2'-deoxycytidine (dFdC, gemcitabine) is a cytidine analogue active against several solid tumor types, such as ovarian, pancreatic and non-small cell lung cancer. The compound has a complex mechanism of action. Because of the structural similarity of one metabolite of dFdC, dFdUMP, with the natural substrate for thymidylate synthase (TS) dUMP, we investigated whether dFdC and its deamination product 2',2'-difluoro-2'-deoxyuridine (dFdU) would inhibit TS. This study was performed using two solid tumor cell lines: the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000. The specific TS inhibitor Raltitrexed (RTX) was included as a positive control. Using the in situ TS activity assay measuring the intracellular conversion of [5-(3)H]-2'-deoxyuridine or [5-(3)H]-2'-deoxycytidine to dTMP and tritiated water, it was observed that dFdC and dFdU inhibited TS. In A2780 cells after a 4h exposure to 1 μM dFdC tritium release was inhibited by 50% but did not increase after 24h, Inhibition was also observed following dFdU at 100 μM.
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CAS 114248-23-6 Gemcitabine Impurity C (EP)

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