Tandutinib hydrochloride (MLN518 hydrochloride) is a potent and selective inhibitor of the FLT3 with an IC 50 of 0.22 μM, and also inhibits c-Kit and PDGFR with IC 50 s of 0.17 μM and 0.20 μM, respectively. Tandutinib hydrochloride can be used for acute myelogenous leukemia (AML) Tandutinib hydrochloride has the ability to cross the blood-brain barrier
In Vitro
Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC 50 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 ( IC 50 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 IC 50 of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Apoptosis AnalysisCell Line: Molm-14 and THP-1 AML cells Concentration: 1 μM Incubation Time: 24 hours, 48 hours, 72 hours, 96 hours Result: Induced apoptosis in FLT3-ITD-positive AML cells. Western Blot AnalysisCell Line: Ba/F3 cells Concentration: 0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM Incubation Time: 30 minutes Result: In Ba/F3 cells expressing different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation.
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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Athymic nude mice injected with Ba/F3 cells Dosage: 60 mg/kg Administration: Oral gavage; daily; for 35 days Result: Caused a statistically significant increase in survival that was extended on average by 20 days.
