Delimotecan (MEN 4901)
is an anticancer prodrug composed of a novel camptothecin analogue (in red, in the figure), a peptide linker and a polysaccaride carrier.

The camptothecin analogue, when released from delimotecan, acts as a potent cytotoxic agent through topoisomerase I enzyme inhibition.

By virtue of its peculiar macromolecular structure, delimotecan is accumulated in the tumor tissue where the active principle is gradually released by the enzyme cathepsin B, overexpressed in infiltrated macrophages and some tumoral cells.

Since human metastatic melanoma cells exhibit a peculiar macrophagic behaviour and express very high levels of cathepsin B, delimotecan is considered to be an extremely interesting candidate for the treatment of advanced stage metastatic melanoma, a highly unmet medical need indication.
Preclinical models of human tumors showed that delimotecan exerts a potent, wide spectrum and long lasting antitumor activity, superior to conventional camptothecins, being effective also against tumors in advanced re-growth phase. In particular, in nude mice bearing human metastatic melanoma xenografts, the selective delimotecan accumulation in the tumor, the intratumoral release of the active moiety, and its potent anti-tumor activity have been demonstrated.

Safety, tolerability and kinetic features of delimotecan (as intravenous infusion) have been assessed in a phase I clinical study, that also gave promising preliminary indications of efficacy. Delimotecan is now ready to enter a phase II trial/proof-of-concept study in patients with advanced metastatic melanoma.