TL02-59

TL02-59 is an Fgr inhibitor (IC₅₀ = 0.03 nM).¹ It is selective for Fgr over the additional Src family kinases LYN, spleen tyrosine kinase (Syk), and HCK (IC₅₀s = 0.1, 470, and 160 nM, respectively), as well as Fes, FMS-related tyrosine kinase 3 (FLT3), p38α 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 = 0.78 and 6.6 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.²

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1. Weir, M.C., Shu, S.T., Patel, R.K., et al. Selective inhibition of the myeloid Src-family kinase Fgr potently suppresses AML cell growth in vitro and in vivo. ACS Chem. Biol. 13(6), 1551-1559 (2018).

2. Mukherjee, A., Epperly, M.W., Fisher, R., et al. Inhibition of tyrosine kinase Fgr prevents radiation-induced pulmonary fibrosis (RIPF). Cell Death Discov. 9(1), 252 (2023).