tcsc2524 Mitoxantrone

Mitoxantrone is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM.

IC50 & Target: IC50: 8.5 μM (PKC)^[1]

In Vitro: Mitoxantrone inhibits PKC in a competitive manner with respect to histone H1, and its K_i value is 6.3 μM and in a non-competitive manner with respect to phosphatidylserine and ATP^[1]. Treatment of B-CLL cells for 48 h with mitoxantrone (0.5 μg/mL) induces a decrease in cell viability. Mitoxantrone induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of mitoxantrone is due to induction of apoptosis^[2]. Mitoxantrone shows cytotoxicity to human breast carcinoma cell lines MDA-MB-231 and MCF-7 with IC₅₀ values of 18 and 196 nM, respectively^[3].

In Vivo: Mitoxantrone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produces a statistically significant number of 60-day survivors (curative effect) in mice with IP implanted L1210 leukemia. In SC implanted Lewis lung carcinoma, mitoxantrone and ADM administered IV also shows effective antitumor activities and produces a 60% and a 45% ILS, respectively.^[4].