TL02-59 dihydrochloride is an orally active inhibitor of Src-family kinase Fgr (IC50: 0.03 nM).

FGR:0.03 nM , Hck:160 nM , Lyn:0.1 nM

in TF-1 cells, TL02-59 dihydrochloride (0.1-1000 nM; 6 hours) potently inhibits Fgr autophosphorylation , 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. TL02-59 dihydrochloride induces growth arrest in primary AML bone marrow samples. TL02-59 dihydrochloride inhibits the growth and induced apoptosis of AML cell lines expressing this kinase with single-digit nM potency.

TL02-59 (oral; 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.