In Vitro: Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants. Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells. In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC50 of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib. Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with an IC50 of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways.
In Vivo: Tandutinib (60 mg/kg; oral gavage; daily; for 35 days; athymic nude mice) treatment causes a statistically significant increase in survival that was extended on average by 20 days.