TAK-659

TAK-659 is a highly potent, selective, reversible and orally available dual inhibitor of spleen tyrosine kinase (SYK) and fms related tyrosine kinase 3 (FLT3), with an IC₅₀ of 3.2 nM and 4.6 nM for SYK and FLT3, respectively. TAK-659 induces cell death in tumor cells but not in nontumor cells, and with potential for the treatment of chronic lymphocytic leukemia (CLL)^[1][2][3][4]. IC50 & Target: IC50: 3.2 nM (Syk), 4.6 nM (FLT3)^[1] In Vitro: TAK-659 inhibits cellular proliferation in SYK-dependent DLBCL and FLT3-dependent AML cell lines^[1][3].
TAK-659 (5 µM; 1-24 hours) induces Casp3 activation in the LMP2A/MYC cells which was readily apparent at 4 h and reached maximum levels at 8 h of treatment^[4].
TAK-659 (0.01-10 μM; 1 hour) stimulates expression of phospho-Syk at Tyr525 and Tyr352 and phospho-ERK1/2 increased in Ramos cells^[2].
In Vivo: TAK-659 (100 mg/kg/day; p.o.; for 10 days) treatment totally abrogates splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments^[4].
TAK-659 treatment kills tumor cells, but not host cells within the spleen and tumors^[4].
TAK-659 treatment abrogates metastasis of tumor cells into bone marrow^[4].