Guadecitabine is a second-generation DNA methyltransferases inhibitor. It is used for research on acute myeloid leukemia and myelodysplastic syndromes.

Exposure to Guadecitabine significantly enhances the expression levels of HLA class I antigens, specifically HLA-A2 allospecificity, and the co-stimulatory molecule ICAM-1 in Mel 275 melanoma cells, indicating an upregulation (p<0.05). Additionally, it notably reduces the methylation levels of CTA promoters in the cancer cells studied, leading to a significant decrease (p<0.01). This exposure also stimulates the expression of previously non-expressed cancer/testis antigens in CTA-negative cancer cells and markedly increases MAGE-A3- and NY-ESO-1-specific mRNA expression across all investigated neoplastic cell histotypes. Furthermore, Guadecitabine's induction of demethylation in MAGE-A1 and NY-ESO-1 promoters shows mean values of 57% and 30% in Mel 195 cells, and 22% and 33% in MZ-1257 RCC cells, respectively.

Guadecitabine effectively inhibits tumor growth with significantly lower toxicity levels, as evident through less weight change in mice, when administered subcutaneously (SQ) compared to intraperitoneal (IP) injections. Although Guadecitabine does not reduce tumor size, it markedly restricts their growth, in contrast to tumors receiving only PBS, which exhibit considerable enlargement [3].