Gemcitabine triphosphate

Gemcitabine triphosphate (dFdCTP) is the active metabolite of Gemcitabine (HY-17026). The mechanism of Gemcitabine triphosphate cell-killing is its competition with cytidine triphosphate during DNA replication, which results in the inhibition of chain elongation. Gemcitabine triphosphate shows a K_i of 11.2 μM against DNA polymerase α and 14.4 μM against DNA polymerase ε. Gemcitabine triphosphate partially inhibits dCMP deaminase and acts as a substrate for DNA synthesis to incorporate into cellular DNA and RNA. Gemcitabine triphosphate disrupts DNA and RNA synthesis, arrests cell cycle in G0/G1 and S phases, triggers apoptosis, reduces tumor cell proliferation. Gemcitabine triphosphate can be used for the research of pancreatic cancer and non-small cell lung cancer^[1][2][3][4]. In Vitro:Gemcitabine triphosphate inhibits replicative DNA polymerases α and ε with K_i values of 11.2 μM and 14.4 μM, respectively^[1].
Gemcitabine triphosphate (0.01-10 μM; short-term incubation) accumulates to 0.01-10 μM in human colon carcinoma cells, with radiation enhancement ratios plateauing at 1.0 μM Gemcitabine (precursor)^[1].
Gemcitabine triphosphate (0.1-10 μM; 48 h) reduces cell viability in H460 human NSCLC cells and BxPC-3 human pancreatic cancer cells in a dose-dependent manner^[3].
Gemcitabine triphosphate (1.8 μM; 24 h) arrests the cell cycle in the S phase in H460 human NSCLC cells and BxPC-3 human pancreatic cancer cells^[3].
Gemcitabine triphosphate (1.8 μM; 48 h) induce caspase-3/7 activation in H460 human NSCLC cells and BxPC-3 human pancreatic cancer cells^[3]. In Vivo:Gemcitabine triphosphate (dFdCTP), the active form generated via consecutive weekly administration for 11 weeks, exerts antitumor effects in female BALB/cAJcl-nu/nu mice bearing pancreatic cancer cells (SUIT-2 orthotopic xenograft model), resulting in a median survival time of 89 days and a survival rate of 40% at the end of the experiment^[2].
Lipid/calcium/phosphate (LCP) nanoparticles loaded with Gemcitabine triphosphate (7.5 μmol/kg; i.v.; every other day for 4 days, followed by daily administration for 3 days) exert potent anti-tumor efficacy in H460 non-small cell lung cancer and BxPC-3 pancreatic cancer xenograft models via caspase-dependent apoptosis, proliferation inhibition and tumor growth arrest^[3].