Mitoxantrone (diacetate)

Mitoxantrone diacetate is a potent topoisomerase II inhibitor. Mitoxantrone diacetate also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM. Mitoxantrone diacetate induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone diacetate shows antitumor activity^[1][2][3][4]. Mitoxantrone diacetate also has anti-orthopoxvirus activity with EC₅₀s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively^[5]. IC50 & Target:IC₅₀: 8.5 μM (PKC)^[1] In Vitro: Mitoxantrone diacetate 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].
Mitoxantrone diacetate (0.5 μg/mL, 48 h) induces a decrease in B-CLL cells. Mitoxantrone diacetate induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of Mitoxantrone diacetate is due to induction of apoptosis^[2].
Mitoxantrone diacetate 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 diacetate (IP, 0-3.2 mg/kg/day) produces a statistically significant number of 60-day survivors at 1.6 mg/kg in mice with IP implanted L1210 leukemia^[4].
Mitoxantrone diacetate (IV, 0-3.2 mg/kg/day) shows effective antitumor activities and produces a 60% ILS (increase in lifespan) at 3.2 mg/kg in SC implanted Lewis lung carcinoma^[4].