CENTRO DI RIFERIMENTO ONCOLOGICO
Technology Transfer Opportunities Contact: Ermes Mestroni emestroni@cro.it
ANTITUMOR GOLD (III) COMPLEXES WITH OLIGOPEPTIDES FUNCTIONALIZED WITH SULFUR DONORS AS IMPROVED SYSTEMS FOR INTRACELLULAR TRANSFER AND DELIVERY Technology Overview - PCT/EP 2009/053296 Some of the most widely employed drugs to treat several types of cancer are platinum based coordination compounds (e.g. Cisplatin, Carboplatin). Despite high effectiveness, the therapy is severely hindered by clinical problems such as severe side effects and frequent occurrence of either intrinsic or acquired resistance to the treatment. University of Padua and CRO have designed highly innovative gold-peptido derivatives with an 500 ca. 33% enormous potential as anticancer 400 inhibition agents because of noticeable in 300 Control vitro and in vivo antitumor AUD6 activity toward different kind of 200 AUD8 tumours, lack of cross-resistance 100 with cisplatin and reduced > 90% 0 adverse side-effects (i.e. D11 D1 D3 D5 D7 D9 D13 inhibition negligible nephrotoxicity, very low acute toxicity). In addition, there is a potential enhanced bioavailability through the di-/tripeptidemediated cellular internalization by exploiting peptide transporters which represent an excellent target for the delivery of pharmacologically-active compounds. In vivo antitumor activity studies on nude mice bearing human breast cancer MDA-MB-231 cells
Advantages These new gold(III) complexes provide an evaluable alternative to cisplatin and other metal-based antineoplastic agents for the following characteristics: √ In vitro citotoxicity at micromolar concentration on several sensible and resistant to cisplatin human tumor cell lines, √ Significant in vivo anticancer activity (test on breast xenograft tumors have shown up of 90% of growth inhibition), √ Lack or very low renal and systemic toxicity, √ Improved intracellular drug transfer and delivery via peptido-mediated cellular
internalization, √ Easy to obtain and stable under phisiological conditions.