Pifithrin-μ

Pifithrin-μ is an inhibitor of p53 and HSP70, with antitumor and neuroprotective activity. IC50 & Target: p53^[1], HSP70^[2] In Vitro: Pifithrin-μ (10 μM) is a p53 inhibitor, which inhibits p53 binding to mitochondria by reducing its affinity to antiapoptotic proteins Bcl-xL and Bcl-2 but has no effect on p53-dependent transactivation, activity of caspases 2, 8, 9 and 10 in a cell-free system, or NF-κB-dependent transcription^[1]. Pifithrin-μ (PES) time- and dose-dependently reduces viability in A549 cells, with IC₅₀s of 44.9 and 25.7 µM at 24 h and 48 h. Pifithrin-μ (20 μM) suppresses the cell migration, induces cell cycle arrest and cell apoptosis in A549 and H460 cells. Pifithrin-μ (10 or 20 µM) inhibits activities of AKT, ERK, and Hsp70 in A549 and H460 cells. Pifithrin-μ (20 µM) sensitizes A549 and H460 cell lines to TRAIL-induced cell proliferation inhibition and apoptosis^[2]. In Vivo: Pifithrin-μ (40 mg/kg, i.p.) shows no protective effect against doses of radiation that cause gastrointestinal syndrome in mice^[1]. Pifithrin-μ (PES, 10 mg/kg) shows antitumor effect in mice bearing A549 cells^[2]. Pifithrin-μ exhibits neuroprotective effect with the P53-inhibitor pifithrin-μ after cardiac arrest in a rodent model^[3].