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Fig. 2 | Clinical Epigenetics

Fig. 2

From: Novel prodrugs of decitabine with greater metabolic stability and less toxicity

Fig. 2

Effects of OR-2003 and OR-2100 on DNA methylation. a DNA demethylation of marker genes by OR-2003 and OR-2100. Methylation levels of an exogenous UCHL1 promoter CpG island and an endogenous OSR2 promoter CpG island were analyzed by qMSP in drug-treated cells (0.0 to 10.0 μM). OR-2003 induced demethylation of these two genes at levels similar to or stronger than that of DAC and that of guadecitabine. OR-2100 induced a demethylation effect similar to or a slightly lower than that of DAC, and stronger than that of guadecitabine. Each qMSP analysis was performed thrice, and the results are represented as mean ± SD. b Genome-wide DNA demethylation by OR-2003 and OR-2100. Genome-wide DNA methylation levels were analyzed using an Infinium Human MethylationEPIC BeadChip in non-treated cells and drug-treated cells (1 μM) and compared. Methylation levels are shown as β-values (0.0 to 1.0). Comparison of 865,918 CpG sites between non-treated cells and treated cells showed that both OR-2003 and OR-2100 induced strong DNA demethylation. c Comparison of demethylated regions among three compounds. The demethylated regions were very similar between DAC and OR-2003, whereas these differed slightly between DAC and OR-2100 and between OR-2003 and OR-2100

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