Didox is a synthetic antioxidant and a potent ribonucleotide reductase (RNR) inhibitor. Didox treatment of mouse bone marrow-derived mast cells (BMMC) reduced IgE-stimulated degranulation and cytokine production, including IL-6, IL-13, TNF and MIP-1a (CCL3). Furthermore, Didox increased expression of the antioxidant genes superoxide dismutase and catalase, and suppressed DCFH-DA fluorescence, indicating reduced reactive oxygen species production[3]. Didox was active against all human and murine AML (Acute Myeloid Leukemia) lines tested with IC50 values in the low micromolar range (mean IC50 37 µM [range 25.89-52.70 µM]). Didox exposure resulted in DNA damage and p53 induction culminating in apoptosis. Didox was well tolerated and effective against preclinical models of AML[4]. Didox induced caspase-dependent multiple myeloma (MM) cell apoptosis[5]. Nuclear translocation of NF-κβ (p65) in response to LPS is inhibited by didox[6].
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