Fig. 2.
Sunitinib and imatinib inhibit unactivated KIT more effectively than activated KIT. Effects of sunitinib (red circles) and imatinib (gold triangles) on activated KIT were assayed in a mixture containing 1.2 mM ATP and 0.25 mg/mL poly(Glu-Tyr); the rate of ATP depletion was followed. Effects of sunitinib (black circles) and imatinib (green triangles) on KIT autoactivation were assayed in a mixture containing 40 nM unactivated KIT and 4 mM ATP for 16 h. Activated KIT resulting from this autoactivation reaction in the presence/absence of inhibitors was estimated based on kinase activity of the activated enzyme. IC50 values were determined as described in Methods.