TS-002266

TS-002266 is a novel, selective small molecule inhibitor of the terminal uridyltransferases TUT4 (ZCCHC11) and TUT7 (ZCCHC6), which are key mediators of RNA stability and miRNA biogenesis. Developed by 128-7 Therapeutics, TS-002266 works by abrogating cellular miRNA uridylation, which in turn reduces the proliferation of MLL-rearranged acute myeloid leukemia (AML) cells and induces changes in cell cycle progression. Mechanistically, the inhibition of TUT4/7 leads to a reduction in BCL-2 mRNA and protein levels and an increase in the expression of BCL-2-regulating miRNAs (such as miR139-5p and miR494-3p), thereby sensitizing AML cells to BCL-2 inhibitors like venetoclax.