Thus, virtual ligand screening of compound libraries targeting the pY-peptide binding pocket of the Stat3 SH2 domain identified for the first time 3 lead compounds that competitively inhibit Stat3 SH2 domain binding to its pY-peptide ligand, selectively target Stat3 vs. Stat1 and induce apoptosis preferentially of breast cancer cells lines with constitutively activated Stat3. Here, STAT3 is linked to breast carcinoma.