Pixantrone

Pixantrone (BBR 2778) dimaleate is a topoisomerase II inhibitor and DNA intercalator, with anti-tumor activity. IC50 & Target: Topoisomerase II^[1] 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^[1].
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^[1].
Pixantrone (100 nM, 24 h) dimaleate may disrupt chromosome segregation because of generating merotelic kinetochore attachments that cause chromosome non-disjunction^[1].
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^[2].
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^[2].
Pixantrone (0.01-10 μM) dimaleate shows potent inhibitory activities against rat 97-116 peptide-specific T cell proliferation^[4].
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^[3].
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^[4].