Pixantrone dimaleate

Pixantrone dimaleate (BBR 2778 dimaleate) is an experimental antineoplastic drug.(In Vitro):Pixantrone (0-10 μM, 72 h) dimaleate induces cell death in multiple cancer cell lines independent of cell cycle perturbation, with IC50s of 37.3 nM, 126 nM and 136 nM for T47D, MCF-10A and OVCAR5 cells, respectively.Pixantrone (25-500 nM, 2 4 h) dimaleate induces DNA damage at high concentration of 500 nM and induces severe chromosomal aberrations and mitotic catastrophe in PANC1 cells.Pixantrone (100 nM, 24 h) dimaleate may disrupt chromosome segregation because of generating merotelic kinetochore attachments that cause chromosome non-disjunction.Pixantrone (0-100 μM, 72 h) dimaleate potently inhibits growth of human leukemia K562 cells, etoposide-resistant K/VP.5 cells, MDCK and ABCB1-transfected MDCK/MDR cells with IC50s of 0.10 μM, 0.56 μM, 0.058 μM and 4.5 μM, respectively.Pixantrone (0.01-0.2 μM) dimaleate leads to a concentration-dependent formation of linear DNA through acting on topoisomerase Iiα and produces semiquinone free radicals in an enzymatic reducing system, although not in a cellular system, most likely due to low cellular uptake.Pixantrone (0.01-10 μM) dimaleate shows potent inhibitory activities against rat 97-116 peptide-specific T cell proliferation.(In Vivo):Pixantrone (i.v., 27 mg/kg, every 7 days, three times) dimaleate does not worsen pre-existing moderate degenerative cardiomyopathy, causes minimal cardiotoxic in mice following repeated treatment cycles and results in less mortality than mitoxantrone in doxorubicin-pretreated mice.Pixantrone (i.v., 16.25 mg/kg, every week, three times) dimaleate modulates Lymph node cells (LNC) responses, affacts T cell subpopulations in TAChR-immunized Lewis rats and also shows preventive and therapeutic effect in experimental autoimmune myasthenia gravis (EAMG) rats.