Novel anthracycline prodrugs

This paper highlights recent patents in the field of anthracycline prodrugs, which are employed in tumour-selective chemotherapy. The prodrugs can be a part of a two-step directed enzyme prodrug therapy (DEPT), which involves the localisation of the prodrug trigger at the tumour site, followed hy the administration of the prodrug and subsequent tumour-selective anthracycline release. In most cases this trigger is an enzyme. which is indirectly localised by an antibody (ADEPT) or a gene encoding for an enzyme (GDEPT). Furthermore, anthracyclines can be targeted to the tumour site via prodrug monotherapy. Anthracycline prodrugs exploiting differences in physiological conditions, such as a lower pH and a lower oxygen tension in tumour tissue compared to healthy tissue, tumour-specific enzymes, such as plasmin, cathepsin B and beta -glucuronidase are discussed. Finally, prodrugs are reviewed that home to tumour-selective receptors. Promising advances in this field concern receptors that are required for angiogenesis.