indotecan

Indotecan (LMP400) is a small molecule indenoisoquinoline that acts as a non-camptothecin inhibitor of DNA topoisomerase 1 (TOP1). Developed by the National Cancer Institute (NCI), it was designed to overcome the limitations associated with traditional camptothecins, such as chemical instability at physiological pH, short plasma half-life, and susceptibility to multidrug-resistance (MDR) transporters like ABCG2. Indotecan works by intercalating into DNA and stabilizing the Top1-DNA covalent cleavage complexes, which prevents DNA religation and leads to persistent DNA damage and subsequent apoptosis. It has been evaluated in Phase I clinical trials for the treatment of advanced or relapsed solid tumors and lymphomas, demonstrating a distinct DNA cleavage site preference and greater stability of the cleavage complexes compared to camptothecin derivatives.

Other names

indenoisoquinoline LMP400