The phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway is constitutively activated in a substantial proportion of prostate tumors and is considered a key mechanism supporting progression toward an androgen-independent status, for which no effective therapy is available. Therefore, PI3K inhibitors, alone or in combination with other cytotoxic drugs, could potentially be used to treat cancer with a constitutive activated PI3K/Akt pathway. To selectively target advanced prostate tumors with a constitutive activated PI3K/Akt pathway, a prostate cancer-specific PI3K inhibitor was generated by coupling the chemically modified form of the quercetin analogue LY294002 (HO-CH₂-LY294002, compound 8) with the peptide Mu-LEHSSKLQL, in which the internal sequence HSSKLQ is a substrate for the prostate-specific antigen (PSA) protease. The result is a water-soluble and latent PI3K inhibitor prodrug (compound 11), its activation being dependent on PSA cleavage. Once activated, the L-O-CH₂-LY294002 (compound 10) can specifically inhibit PI3K in PSA-secreting prostate cancer cells and induce apoptosis with a potency comparable to that of the original LY294002 compound.