TAE684 induces regression of established H2228 xenograft tumors. (A) TAE684 inhibits H2228 but not A549 xenograft tumor growth. A total of 5 x 106 H2228 or A549 cells were implanted subcutaneously (sc) into nude mice. When the average tumor size reached 300 mm3 (H2228) or 100 mm3 (A549), mice were randomized into different treatment groups. TAE684 was administered per os daily at the indicated doses or vehicle (10% 1-methyl-2-pyrrolidinone/90% PEG30). n = 10 for each group. P= 7.6 x 10-32 (control vs TAE684 5 mg/kg), P = 8 x 10-11 (TAE684 5 vs 15 mg/kg). (B) TAE684 inhibits EML4-ALK signaling in H2228 xenograft tumors. Established H2228 xenograft tumors were treated with 15 mg/kg TAE684, cell lysates were prepared at the indicated time, and Western blot analysis was performed to measure phosphorylated Akt, ERK, and STAT3. (C, D) TAE684 inhibits proliferation and induces apoptosis of H2228 tumor cells. Established H2228 xenogaft tumors were treated with 15 mg/kg TAE684, and Ki-67 IHC was performed at the indicated time to measure cell proliferation. For apoptosis analysis, tumors were collected at the indicated time after dosing, and tumor cells were stained with annexin V (n = 3 for each time point).