Nemorubicin

Abstract

Nemorubicin is a 3'-deamino-3'[2-(S)-methoxy-4-morpholinyl]derivative of doxorubicin. This derivative has been synthesized in the early 1990s by the Farmitalia CarloErba Research Center in Italy. The idea was to develop doxorubicin analogues able to circumvent the emergenceof chemoresistance, in particular the multi-drug resistance. The drug was reported to be active in vitroagainst both murine and human tumor cells resistant to doxorubicin. Similar results were obtained whenthe drug was administered in vivo to mice bearing multi-drug resistant tumors. The compound retained thesame activity also in alkylating agents and topoisomerase II resistant tumors and showed an increased potencyrelative to the parent drug doxorubicin. It is metabolized via P450 CYP3A enzyme to an extremely cytotoxicderivative. Both nemorubicin and its metabolite have a mechanism of action different from that ofdoxorubicin, with a key role played by the nucleotide excision repair system. The drug is activelytested in clinics as a single agent or in combination with cisplatin.