Dacarbazine(DTIC-Dome; DTIC) is an antineoplastic agent. It has significant activity against melanomas.
Target: Nucleoside antimetabolite/analog
Approved: May 1975
Dacarbazine (DTIC) is the only single-agent approved by the Food and Drug Administration for treating metastatic melanoma. With DTIC as single agent, an approximately 20% objective response rate can be achieved with median response duration of 5 to 6 months and complete response rates of 5% [1]. Dacarbazine (DTIC) has activity in advanced previously untreated pancreatic islet cell tumors [2]. In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75) [3].
 

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.