GSK-3680532

GSK-3680532 is a selective small molecule inhibitor of DNA methyltransferase 1 (DNMT1) developed by GSK. It functions as a hypomethylating agent (HMA) but, unlike nucleoside analogs such as azacitidine or decitabine, it directly inhibits the DNMT1 enzyme without requiring incorporation into DNA. In preclinical studies for acute myeloid leukemia (AML), GSK-3680532 has shown the ability to induce DNA hypomethylation and promote apoptosis, particularly in cells where the deubiquitinating enzyme USP48 is lost. This synergy suggests that GSK-3680532 may be effective in combination therapies targeting chromatin remodeling and DNA damage repair pathways.