TL02-59

TL02-59 is an Fgr inhibitor (IC50 = 0. nM). It is selective for Fgr over the additional Src family kinases LYN, spleen tyrosine kinase (Syk), and HCK (IC50s = 0. 470, and 160 nM, respectively), as well as Fes, FMS-related tyrosine kinase 3 (FLT3), p38alpha MAPK, and TAOK3 (IC50s = 290, 633, 126, and 509 nM, respectively). TL02-59 selectively inhibits the growth of MV4-11 and MOLM-14 acute myeloid leukemia (AML) cells (IC50s = 0. and 6. nM, respectively), which are positive for FLT3 bearing internal-tandem duplication (FLT3-ITD+) and express several active non-receptor tyrosine kinases, over THP-1 AML cells (IC50 = >3,000 nM) which do not bear those oncogenic transformations. In vivo, TL02-59 (10 mg/kg) decreases the percentage of engrafted CD45+/CD33+ MV4-11 cells in the bone marrow and spleen in a mouse xenograft model. It reduces radiation-induced pulmonary fibrosis in mice when administered at a dose of 10 mg/kg.. Solulibility: DMSO: Sparingly soluble: 1-10 mg/ml: .