The binding of insulin-like growth factor 1 (IGF-1) to the IGF-1 receptor (IGF-1R) initiates a cascade of reactions that promote cell growth and transformation by activating the PI3K/Akt signaling pathway, inhibiting apoptotic pathways, and mediating mitogenic actions. Overexpression of IGF-1R confers tumorigenic potential to cells as well as protection from apoptosis. AG-1024 is a selective inhibitor of IGF-1R that inhibits insulin-stimulated cellular proliferation and IGF-1R autophosphorylation with IC50 values of 0.4 and 7 μM, respectively. At 10 nM, AG-1024 can inhibit proliferation and induce apoptosis in human breast cancer MCF-7 cells, and it inhibits autocrine growth of human prostate cancer DU145 cells with an IC50 value of 2.5 μM.
