Chemical research in toxicology
-
Chem. Res. Toxicol. · Aug 2016
Rethinking Drugs from Chemistry to Therapeutic Opportunities: Pixantrone beyond Anthracyclines.
Pixantrone (6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione) has been approved by the European Medicines Agency for the treatment of refractory or relapsed non-Hodgkin's lymphoma (NHL). It is popularly referred to as a novel aza-anthracenedione, and as such it is grouped with anthracycline-like drugs. Preclinical development of pixantrone was in fact tailored to retain the same antitumor activity as that of anthracyclines or other anthracenediones while also avoiding cardiotoxicity that dose-limits clinical use of anthracycline-like drugs. ⋯ For example, pixantrone causes mis-segregation of genomic material in cancer cells and inhibits formation of toxic anthracycline metabolites in cardiac cells. Understanding the differences between pixantrone and anthracyclines or mitoxantrone may help one to appreciate how it worked in the phase 3 study that led to its approval in Europe and how it might work in many more patients in everyday clinical practice, were it properly perceived as a drug with its own characteristics and therapeutic potential. The road is rocky but not a dead-end.