TL02-59

TL02-59 is an orally active, selective Src-family kinase Fgr inhibitor with an IC₅₀ of 0.03 nM. TL02-59 inhibits Lyn and Hck with IC₅₀s of 0.1 nM and 160 nM, respectively. TL02-59 potently suppresses acute myelogenous leukemia (AML) cell growth^[1]. IC50 & Target: IC50: 0.03 nM (Fgr), 0.1 nM (Lyn) and 160 nM (Hck)^[1] In Vitro: TL02-59 (0.1-1000 nM; 6 hours) potently inhibits Fgr autophosphorylation in TF-1 cells, with paritial inhibition at 0.1-1 nM and complete inhibition above 10 nM. Hck, Lyn and Flt3 are inhibited in the 100 to 1000 nM range^[1].
TL02-59 inhibits the growth and induced apoptosis of AML cell lines expressing this kinase with single-digit nM potency^[1].
TL02-59 induces growth arrest in primary AML bone marrow samples^[1].
In Vivo: TL02-59 (oral administration; 1 and 10 mg/kg; for three weeks) completely eliminates AML cells from the spleen and peripheral blood in a mouse model of AML, while dramatically suppressing bone marrow involvement^[1].
TL02-59 has a t_1/2 of 5.7 h by i.v injection and 6.5 h by p.o. administration, respectively^[1].