Topisomerase II inhibitors

Patent Pending Small molecules that target type II topoisomerase are divided into two classes: inhibitors and poisons. Inhibitors of type II topoisomerase include HU-331, ICRF-187, ICRF-193, and mitindomide. These molecules work by inhibiting the ATPase activity by acting as noncompetitive inhibitors of ATP. This has been shown through structural studies (Classen et al. Proceedings of the National Academy of Science, 2005) and biochemical studies performed by the Lindsley group. Poisons of type II topoisomerases include etoposide, novobiocin, quinolones (including ciprofloxacin), and teniposide. These small molecules target the DNA-protein complex. Some of these molecules lead to increased cleavage, whereas others, such as etoposide, inhibit religation.