Figure 4

A-928605 abrogates modifications of IGF pathway signaling proteins in vitro and is efficacious in the CD8-IGF1R xenograft flank model in vivo. A, One hour of 1 mM A-928605 treatment in vector control and CD8-IGF1R cells results in inhibition of phosphorylation of the IGF1R cytotail and the immediate downstream pathway effectors AKT and ERK1/2. Cyclin D1 is a transcriptional target of the IGF signaling pathway and is therefore not affected by this one hour treatment. B, 24-hours of 1 mM A-928605 treatment in vector control and CD8-IGF1R cells results in a significant decrease in Cyclin D1 expression as seen here and in the microarray results (Figure 3). C, Beginning on day 17 post tumor cell injection, mice were dosed intraperitoneally with A-928605 at 50 mg/kg, twice daily (b.i.d)., or its vehicle for 10 days. At the end of the dosing schedule, the %T/C (A-928605 vs. vehicle) was 21 (P < 0.00001).