Fig. 3. CCT245718 directly binds to and inhibits FLT3 activation.
a Inhibition of FLT3 by CCT245718. FLT3 was immunoprecipitated from MV-4-11 cells treated with 1.25 and 2.5 µM of CCT245718 for 2 h. Phosphorylation of FLT3 was determined through western blotting with phosphotyrosine antibodies. b CCT245718 binds to FLT3 mutants. Binding constants (KD values) of CCT245718 with FLT3 (D835Y) and FLT3 (ITD) were determined using a competition binding assay. c Superimposition of best-docked pose (green) of CCT245718 on the co-crystalized ligand, ACC220 (cyan) in the active site of FLT3 kinase domain (grey cartoon). Hydrogen bonding is shown with the dotted yellow lines. d Superimposition of best-docked pose (green) of CCT245718 on co-crystal ligand (cyan) in the active site of Aurora A kinase domain (grey cartoon). Hydrogen bonding is shown with the dotted yellow line.