Smart Pro-Drugs of Serine Protease Inhibitors

A prodrug represented by formula (I) or a solvate, pharmaceutically functional derivative or pharmaceutically acceptable salt thereof:

• A-G (I)
• wherein
• A represents a peptidyl moiety, 2-10 amino acid residues in length, that is a substrate for an activating protease which is associated with tumors;
• A and G are covalently linked by a bond that is cleaved by the activating protease;
• and
• G represents a dipeptidyl proteosome inhibitor moiety that, when released from the prodrug by cleavage by the activating protease, inhibits the proteolytic activity of a proteosome with a Ki of 100 nM or less,
• wherein, the dipeptidyl proteosome inhibitor moiety G, when cleaved from A by the activating protease, undergoes reversible cyclization-dependent inactivation over time.