Sabarubicin

• THE FIRST DISACCHARIDE ANTHRACYCLINE

• TOPOISOMERASE II INHIBITOR

• ANTI-CANCER AGENT FOR SOLID TUMOURS

• REMARKABLY POTENT AGAINST PULMONARY MICROCYTOMA

Sabarubicin is a third generation anthracycline featuring a disaccharide moiety in place of the conventional monosaccharide chain. The chemical structure was defined, with the aid of computer-assisted molecular modelling, to increase the number of atomic contacts of the sugar moieties within the minor groove of the DNA thus increasing the stability of the ternary molecular complex: DNA-drug-topoisomerase II. Actually Sabarubicin is a potent topoisomerase II inhibitor, and a strong inducer of DNA breaks and apoptosis in human tumoral cells.

Sabarubicin exerts a notable antitumoral activity in a vast series of human tumours (gynaecological, lung, prostate) xenografted onto nude mice. Its activity spectrum is wider than that of doxorubicin and other anthracyclines currently in use. Sabarubicin was found to be active in doxorubicin-resistant tumour models, too. Moreover, sabarubicin has been proved to be less liable for cardiotoxic effects than other drugs in the class. Two Phase I clinical trias, under E.O.R.T.C. coordination, and six different Phase IIa studies to test the drug activity against solid tumours (ovary, breast, prostate, lung, sarcoma) have been conducted. Sabarubicin showed efficacy against the whole tumour type range, however outstanding effects were observed in patients suffering from small cell lung cancer (also known as microcytoma), a highly aggressive neoplasia, whose therapy did not see major progresses in the latest 30 years.

Accordingly, sabarubicin is currently evaluated, in combination with cisplatin, in microcytoma-extensive disease patients, as the primary indication. The project ended phase II.