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

Exposure to Guadecitabine significantly (p<0.05) up-regulates the constitutive levels of expression of HLA class I antigens, HLA-A2 allospecificity, and of the co-stimulatory molecule ICAM-1, on Mel 275 melanoma cells. Guadecitabine induces a significant (p<0.01) reduction in the constitutive methylation levels of CTA promoters in investigated cancer cells. Exposure to Guadecitabine induces the expression of investigated cancer/testis antigens in CTA-negative cancer cells. Guadecitabine induces strongly up-regulates the constitutive levels of MAGE-A3- and NY-ESO-1-specific mRNA expression in neoplastic cells of all histotypes investigated. Mean values of the percentage of demethylation induced by Guadecitabine in MAGE-A1 and NY-ESO-1 promoters are 57 and 30 %, in Mel 195, and 22 and 33 % in MZ-1257 RCC cells, respectively [2].

Guadecitabine is effective at retarding tumor growth. Guadecitabine induces much less toxicity as determined by mouse weight changes when given subcutaneously (SQ) compare to that with IP injections. While the tumors do not shrink in size with Guadecitabine treatment, they experience very minimal growth while the tumors treated with PBS only show substantial growth [3].