Guadecitabine sodium is a inhibitor of second-generation DNA methyltransferases (DNMT) .

Treatment of HCT116 colorectal carcinoma cells with Guadecitabine sodium (SGI-110 sodium) demonstrated a dose-dependent increase in p16 expression after 6 days. Additionally, there was a similar increase in p16 protein levels in both T24 and HCT116 cells when treated with Guadecitabine sodium or 5-aza-CdR for 3 days. This effect suggests Guadecitabine sodium's effectiveness in inhibiting DNA methylation and stimulating p16 expression at both mRNA and protein levels, akin to 5-aza-CdR. Further, Guadecitabine sodium inhibited DNA methylation in the 5′-region and induced the expression of the p16 gene in T24 and HCT116 cells at concentrations comparable to those of 5-aza-CdR. The induction of p16 expression by both agents was associated with demethylation at the 5′-end region of the gene in both cell lines. In terms of toxicity, Guadecitabine sodium was slightly less toxic than 5-aza-CdR at concentrations up to 1 μM, but displayed similar toxicity levels at 10 μM concentration[1].

Guadecitabine sodium (10mg/kg) effectively reduces DNA methylation, retards tumor growth, and demonstrates a toxicity level comparable to 5-Aza-CdR. It successfully reactivates the expression of the heavily methylated p16 gene in parent EJ6 cells and reduces DNA methylation at the p16 promoter region in vivo. Notably, Guadecitabine sodium exhibits better tolerance compared to 5-Aza-CdR in vivo[2].