OTS447

OTS447 is a highly potent and selective small molecule inhibitor of FMS-like tyrosine kinase 3 (FLT3), developed by OncoTherapy Science for the treatment of acute myeloid leukemia (AML). It specifically targets FLT3 mutations, including internal tandem duplications (ITD) and tyrosine kinase domain (TKD) mutations, which are common drivers of resistance in AML patients treated with existing FLT3 inhibitors like gilteritinib. OTS447 demonstrates sub-nanomolar inhibitory activity (IC50 of 0.19 nM) and shows efficacy against FLT3-ITD-TKD double mutants, such as D835Y and F691I. By blocking FLT3 autophosphorylation and downstream signaling pathways including STAT5, ERK, and AKT, the compound induces apoptosis in leukemic cells and has shown significant anti-tumor activity in mouse xenograft models.