A-419259 is an inhibitor of Src family kinases, including Src, LCK, Lyn, and Hck (IC50s = 9, <3, <3, and 11.26 nM, respectively)., It is selective for these kinases over c-Abl (IC50 = 3,000 nM) and PKC (IC50 = >33 μM). A-419259 inhibits growth of Philadelphia chromosome-positive (Ph+) K-562 and Meg-01 myeloid leukemia cells (IC50s = 0.1-0.3 and 0.1 μM, respectively), but not Ph- TF-1 and HEL cells. It induces apoptosis in K-562 cells in a concentration-dependent manner. A-419259 (300 nM) inhibits differentiation of murine embryonic stem cells while maintaining pluripotency. It reduces the total number of acute myeloid leukemia (AML) cells, as well as AML stem cells, in the bone marrow and spleen in mouse patient-derived xenograft (PDX) models of AML when administered at a dose of 30 mg/kg twice daily.
