Tandutinib

Tandutinib (MLN518) is a potent and selective inhibitor of the FLT3 with an IC₅₀ of 0.22 μM, and also inhibits c-Kit and PDGFR with IC₅₀s of 0.17 μM and 0.20 μM, respectively. Tandutinib can be used for acute myelogenous leukemia (AML)^[1][2]. Tandutinib has the ability to cross the blood-brain barrier^[3]. IC50 & Target: IC50: 0.22 μM (FLT3), 0.17 μM (c-Kit) and 0.20 μM (PDGFR)^[1] 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^[1].
Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells^[1].
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^[1].
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^[1].
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^[1].