Topoisomerase I inhibitor 17

TopoisomeraseI inhibitor 17 (Compound 7h) is an inhibitor of TopoisomeraseI (Top1) . It reduces DDX5 and reverses the locking effect of DDX5 on Top1 activity. This compound induces Top1-mediated DNA damage and promotes reactive oxygen species (ROS) production. It triggers apoptosis by decreasing anti-apoptotic proteins XIAP, Bcl-2, and Survivin, while increasing pro-apoptotic proteins Bax and γH2AX. Moreover, TopoisomeraseI inhibitor 17 halts progression at the G2/M checkpoint, leading to cell cycle arrest. It significantly impairs colorectal cancer cell colony formation and migration, and effectively reduces tumor size in human PDX tumor mouse models.