P8-D6

P8-D6 is a novel small molecule dual topoisomerase I and II poison belonging to the aza-analogous benzo[c]phenanthridine class. Developed by researchers at Kiel University and Hannover Medical School, it functions by covalently stabilizing the enzyme-cleaved DNA complexes of both topoisomerase I and II. This stabilization prevents the religation of DNA strands, leading to an accumulation of permanent single- and double-strand breaks that trigger apoptotic cell death. Preclinical studies have demonstrated that P8-D6 possesses high potency across various malignancies, including cervical, ovarian, and breast cancers, as well as multiple myeloma. Notably, P8-D6 has shown superior pro-apoptotic activity compared to standard chemotherapeutics like cisplatin and acts as a potent radiosensitizer, significantly enhancing the antitumor response to radiotherapy in cervical carcinoma models. It is characterized by a simple two-step synthesis and favorable solubility and stability properties.

Other names

aza-analogous benzo[c]phenanthridine