Expression profiling of DNMT1 inhibitors in HCT116 cells

Epigenetic changes accompany tumorigenesis and are required for tumor maintenance. Modulation of DNA methylation state, histone acetylation, and histone methylation, as well as reversal of disease-associated epigenetic state aberrations, can be disruptive to malignant disease progression. We produced lipophilic prodrugs of decitabine, which is a DNA methyltransferase inhibitor and is efficacious in treatment of myelodysplastic syndromes when dosed subcutaneously. Comparison of parent and prodrug activities in vitro and in vivo revealed comparable effects and unveiled several novel features of nucleoside analog molecular activity in vitro.

24