Topovale (ARC111) is a potent inhibitor of topoisomerase I. Topovale inhibits hypoxia-mediated accumulation of hypoxia-inducible factor-1alpha. Topovale exhibited low nM cytotoxicity against a panel of cancer cells. Topovale cytotoxicity as well as Topovale-induced apoptosis was reduced > 100-fold in CPT-resistant topoisomerase I (TOP1)-deficient P388/CPT45 cells as compared with P388 cells.