Topotecan

Topotecan is a topoisomerase I inhibitor and a semisynthetic derivative of camptothecin. Under normal conditions, topoisomerase I temporarily cuts one strand of DNA during replication or transcription to relieve torsional stress, then rejoins it. Topotecan binds to the topoisomerase I-DNA complex and stabilizes the cleaved but unrejoined state. When the replication fork passes through these transient single-strand breaks, the opposing strand cannot withstand the mechanical stress generated by fork progression and is forcibly broken, resulting in double-strand DNA breaks that ultimately trigger apoptosis.