Pifithrin-α is a reversible inhibitor of p53-mediated apoptosis and p53-dependent gene transcription such as cyclin G, p21/waf1, and mdm2 expression. It enhances cell survival after genotoxic stress such as UV irradiation and treatment with cytotoxic compounds including doxorubicin, etopoxide, paclitaxel, and cytosine-β-D-arabinofuranoside. Pifithrin-α protects mice from lethal whole body γ-irradiation, and does not induce visible tumors.
Protects against neuronal death in models of stroke and neurodegenerative disorders. Pifithrin-α is also an aryl hydrocarbon receptor (AHR) agonist, which leads to the upregulation of AHR target gene CYP1A1 (EC50 = 1.1 μM).
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