Figure 2

A-928605 is a potent inhibitor of IGF signal transduction as seen in a model transformed cell line. A, Parental NIH 3T3 cells compared to the vector control and CD8-IGF1R lines show a strong pIGF1R signal in the CD8-IGF1R line. All cells were grown in normal growth media containing 10% FBS. B, Cells were treated for 1 hour with A-928605 in a dose response analysis as shown. The CD8-IGF1R fusion protein runs as a doublet [25]. C and D, Three day proliferation assay in the NIH-3T3 vector control cells (C) or CD8-IGF1R cells (D) with increasing amounts of six clinical small molecule inhibitors and A-928605. Compounds were run in duplicate at each indicated concentration. Results are representative of 5 separate assays. Intended targets of each small molecule inhibitor are as follows: lapatinib, ERBB2 and EGFR; gefitinib, EGFR; dasatinib, ABL and SRC; Sorafinib, multi-targeted; imatinib, ABL and KIT; erlotinib, EGFR.