Mitoxantrone (hydrochloride)

Mitoxantrone is an inhibitor of DNA topoisomerase IIα and HIV-1 integrase (IC₅₀s = 5.3 and 3.8 μM, respectively).^1,2 It intercalates into DNA in a cell-free assay when used at a concentration of 2 µM, as well as inhibits DNA synthesis and induces DNA-protein crosslinks in vitro in a concentration-dependent manner.^1,3 Mitoxantrone inhibits the growth of K562 leukemia and K562-derived etoposide-resistant K/VP.5 cells (IC₅₀s = 0.42 and 1.68 µM, respectively).¹ It also inhibits the membrane fusion of a mixed population of HEK293T cells expressing either angiotensin-converting enzyme 2 (ACE2) or the extracellular domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein, also known as surface glycoprotein.⁴ Mitoxantrone (0.2 µM) inhibits the entry of SARS-CoV-2 into Vero E6 cells. Formulations containing mitoxantrone have been used in the treatment of cancer and multiple sclerosis.

WARNING This product is not for human or veterinary use.

1. Hasinoff, B.B., Liang, H., Wu, X., et al. The structure-based design, synthesis and biological evaluation of DNA-binding bisintercalating bisanthrapyrazole anticancer compounds. Bioorg. Med. Chem. 16(7), 3959-3968 (2008).

2. Carlson, H.A., Masukawa, K.M., Rubins, K., et al. Developing a dynamic pharmacophore model for HIV-1 integrase. J. Med. Chem. 43(111), 2100-2114 (2000).

3. Fox, M.E., and Smith, P.J. Long-term inhibition of DNA synthesis and the persistence of trapped topoisomerase II complexes in determining the toxicity of the antitumor DNA intercalators mAMSA and mitoxantrone. Cancer Res. 50(18), 5813-5818 (1990).

4. Zhang, Q., Radvak, P., Lee, J., et al. Mitoxantrone modulates a heparan sulfate-spike complex to inhibit SARS-CoV-2 infection. Sci. Rep. 12(1), 6294 (2022).