Gemcitabine(LY-188011; NSC 613327) is a DNA synthesis inhibitor with IC50 of 50 nM, 40 nM, 18 nM and 12 nM in PANC1, MIAPaCa2, BxPC3 and Capan2 cells, respectively.
IC50 Value: 50 nM( PANC1); 40 nM(MIAPaCa2); 18 nM(BxPC3 ); 12 nM(Capan2)
Target: Nucleoside antimetabolite/analog
Gemcitabine is converted intracellularly to the active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis. Gemcitabine inhibits proliferation BxPC-3 pancreatic cancer cell line with IC50 of 0.06 μM.

5-Azacytidine  5-Azacitidine(5-AzaC) is a nucleoside analogue of cytidine that specifically inhibits DNA methylation by trapping DNA methyltransferases.

IC50 Value: Azacitidine inhibits the L1210 cells growth with IC50 and of 0.019 μg/mL.
Target: DNMT
in vitro: Azacitidine is widely used to demonstrate the correlation between loss of methylation in specifc gene regions and activation of the associated genes. After incorporation into DNA, Azacitidine inhibits DNA methyltransferase noncompetitively, causing a block in cytosine methylation in newly replicated DNA but not in resting, nondividing cells[1]. Azacitidine induces differentiation of Friend Erythroleukemia Cell C3H10T1/2 with myotube formation[2]. Azacitidine can be activated to the nucleoside triphosphate and incorporate into both DNA and RNA, leading to inhibition of DNA, RNA and protein synthesis in normal eukaryotic cells and in cancer cell lines, which could finally leads to cell death. Azacitidine also inhibits the incorporation of purine metabolites into macromolecules. Azacitidine inhibits the L1210 cells growth with IC50 and of 0.019 μg/mL[3] .
in vivo: Azacitidine inhibits polynucleotide synthesis in leukemic BDF1 mice[3] . Azacitidine (3 mg/kg, i.p.) increases the mean survival time in leukemic BDF1 mice inoculated with Ll210 ascites tumor cells. Azacitidine markedly suppresses all enzymes activity in the polyamine-biosynthetic pathway, including ornithine decarboxylase activity. putrescine-dependent S-adenosyl-L-methionine decarboxylase activity, and spermidine-dependent S-adenosyl-L-methionine decarboxylase activity. Azacitidine also inhibits the accumulations of polyamines in leukemic mice[4].
Clinical trail: A Phase III study to the Azacitidine on clinically significant adverse cardiovascular and cerebrovascular events in high-risk subjects undergoing coronary artery bypass graft (CABG) surgery has been completed.