Mitoxantrone-d8 is intended for use as an internal standard for the quantification of mitoxantrone by GC- or LC-MS. Mitoxantrone is an anthraquinone that intercalates in DNA and inhibits topoisomerase II (IC50 = 5.3 μM), thus inhibiting cell proliferation.1,2 It also inhibits HIV-1 integrase (IC50 = 3.8 μM).3 Mitoxantrone is exported from cells in an ATP- and glutathione-dependent manner by multidrug resistance protein-1.4 Formulations containing mitoxantrone have been used in the treatment of cancer and multiple sclerosis.5,6,7
|1. 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).|2. 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).|3. 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).|4. Morrow, C.S., Peklak-Scott, C., Bishwokarma, B., et al. Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol. Pharmacol. 69(4), 1499-1505 (2006).|5. Garcia, J.A., and Rini, B.I. Castration-resistant prostate cancer: Many treatments, many options, many challenges ahead. Cancer 118(10), 2583-2593 (2012).|6. Lu, E., Wang, B.W., Guimond, C., et al. Safety of disease-modifying drugs for multiple sclerosis in pregnancy: Current challenges and future considerations for effective pharmacovigilance. Expert Rev. Neurother. 13(3), 251-260 (2013).|7. Marriott, J.J., Miyasaki, J.M., Gronseth, G., et al. Evidence report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis. Neurology 74(18), 1463-1470 (2010).