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Pifithrin-α is a synthetic, water-soluble and stable inhibitor of p53 [1].

Pifithrin-α is firstly found to block the activation of p53-responsive lacZ in ConA cells and reduce activation of endogenous cellular p53-responsive genes. In MEF cells transformed with E1a+ras, 10μM Pifithrin-α can inhibit the apoptosis of the cells and this anti-apoptotic activity is p53-dependent. Pifithrin-α also inhibits the growth arrest of human diploid fibroblasts induced by DNA damage but has no effect on p53-deficient fibroblasts. In addition, Pifithrin-α induces G2-arrest of cells after gamma irradiation [1].

Moerover, Pifithrin-α can also induce cell cycle arrest and growth arrest of embryonic stem cells. Treatment of Pifithrin-α significantly downregulates the protein lever of Nanog (a pluripotency marker).It is proved that the inhibition of p53 activity caused by Pifithrin-α has no effect on ES cell viability [2].

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