Biochem/physiol Actions

Reversible: no

Secondary TargetDNA polymerase

Primary TargetDNA

Cell permeable: yes

General description

A bioavailable, moderately toxic, deoxyctytidine analog with anti-metabolite and anti-tumor properties. Shown to be effective against a variety of tumors and blocks the growth of cancer cells in culture (IC ₅₀ = 8.7, 57, 3.7, and 36 nM for L1210, CEM, Caco2, and HeLa cells, respectively). Following its uptake into cells by nucleoside transporters it is phosphorylated to its mono (dFdCMP), di (dFdCDP), and triphosphorylated (dFdCTP) forms by deoxycytidine kinase. dFdCDP and dFdCTP are reported to inhibit the activity of ribonucleotide reductase and impede DNA synthesis and repair mechanisms and induce cell death. Blocks the progression of cells through the G1/S phase. The dFdCTP is shown to compete with endogenous deoxycytidine triphosphate (dCTP) for incorporation into DNA and against CTP into RNA. Gemcitabine is also shown to block mitochondrial DNA polymerase γ. Works synergistically with other chemotherapeutic agents to enhance their cytotoxicity. Its half life is reported to be 42 to 94 min (depending upon the age and sex of the individual).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Hung, S.W., et al. 2012. Cancer Lett.320, 138.Fowler, J.D., et al. 2008. J. Biol. Chem.283, 15339.Mackey, J.R., et al. 1998. Cancer Res.58, 4349.Eda, H., et al. 1998. Cancer Res.58, 1165.Burris III, H.A., et al. 1997. J. Clin. Oncol.15, 2403.Heinemann, V., et al. 1992. Cancer Res.52, 533.Hertel, L.W., et al. 1990. Cancer Res.50, 4417.

Packaging

Packaged under inert gas

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Carcinogenic / Teratogenic (D)