Herein we review our progress on the development of phosphopeptide-based 
prodrugs targeting the SH2 domain of STAT3 to prevent recruitment to cytokine 
and growth factor receptors, activation, nuclear translocation and transcription 
of genes involved in cancer. We developed high affinity phosphopeptides (K I = 
46-200 nM). Corresponding prodrugs inhibited constitutive and IL-6 induced 
Tyr705 phosphorylation at 0.5-1 μM in a variety of human cancer cell lines. They 
were not cytotoxic at 5 μM in vitro but they inhibited tumor growth in a human 
xenograft breast cancer model in mice, accompanied by reduced VEGF expression 
and angiogenesis.