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The Dual Topoisomerase Inhibitor, BN 80927, Is Highly Potent against Cell Proliferation and Tumor Growth

BN 80927 belongs to a novel family of camptothecin (CPT) analogues, the homocamptothecins (hCPTs),1 developed on the concept of topoisomerase (topo) I inhibition and characterized by the unique feature of a seven-membered βhydroxylactone ring. The lower reactivity of the lactone ring results in enhanced plasma stability compared to that of conventional camptothecin analogues such as topotecan and irinotecan. BN 80927, in addition to its topo I poisoning activity, has been shown to be a topoisomerase II catalytic inhibitor.2 We report here the results of studies evaluating the antiproliferative activity of BN 80927 in a panel of human tumor cell lines, including cells overexpressing P-glycoprotein (PgP). We also evaluated the cytotoxicity of BN 80927 on resting cells, because human tumors are a heterogeneous population of cells including cells that are not actively proliferating. Finally, we report the antitumor activity in xenograft models after oral administration of BN 80927.