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Mitoxantrone is a Topoisomerase II inhibitor, an anti-neoplastic drug for leukemia and other types of cancer, and a proven drug for multiple sclerosis.

Topoisomerase regulates and changes the topologic conditions of DNA during transcription. It plays a role in condensation of chromosome, separation of chromatid and the relief of torsional stress etc.

Mitoxantrone suppressed the leukemia via inhibiting DNA synthesis and cell cycle progression. It had effect on different immune cells (e.g. T cell, B cell and macrophage etc.) [1] It interfered with TOPO-II-mediated DNA cleavage and led to multiple DSB (DNA strand breaks), chromatin structure changes etc. [2] In PDA (pancreatic ductal adenocarcinoma) cell line, mitoxantrone affected cell survival with IC50 < 10 nM and targeted USP11 (human ubiquitin-specific peptidase 11). [3] In human dental pulp stem cells and human dermal fibroblasts, mitoxantrone induced apoptosis or premature senescence in a dose –dependent manner. [4]

In clinical trial, mitoxantrone exhibited a significant but partial efficacy in decreasing the chance of multiple sclerosis progression and relapses frequency in patient with worsening RRMS, PRMS and SPMS in a 2 years follow-up study. [5]

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