In vivo efficacy of AC220 in animal tumor models. (A) Inhibition of FLT3 activity in subcutaneous tumor xenografts. Total and phospho-FLT3 were quantitated in lysates from tumors harvested at each time point, and phospho-FLT3 levels normalized relative to the total amount of FLT3. Normalized phospho-FLT3 levels are shown as a percentage of levels in untreated animals. Each group contained 4 animals. (B) Comparison of antitumor efficacy of AC220 and sunitinib in the subcutaneous tumor model at a dose of 10 mg/kg. Day 1 of the study was the first day of treatment, when tumors had reached a size of 450 to 600 mm³. The solid bar indicates the 28-day treatment period. Tumor size was monitored for an additional 61 days after treatment was discontinued, and total study length was 89 days. Each treatment group contained 10 animals, and the time course of tumor size for each individual animal is shown in blue. The average tumor size in the vehicle control groups is shown in black (± SEM) for comparison. Animals were killed if tumor volume reached 1000 mm³. (C) Efficacy of AC220 in a bone marrow transplant model. Kaplan-Meier plots of survival. Day 1 of the study was the day after cells were implanted. The solid bar indicates the treatment period of 30 days. Each treatment group contained 5 animals. Data for the vehicle control group are shown as ■. The study was terminated on day 172.