Pifithrin-u

In addition to its transactivational functions, p53 mediates apoptosis by binding with the anti-apoptotic proteins Bcl-xL and Bcl-2 at the mitochondrial surface.{19632,19633} Pifithrin-? (PFT-?) is an inhibitor of p53-mediated apoptosis, preventing p53 binding to Bcl-xL and Bcl-2 at the mitochondria without affecting p53 transactivational activities{19632} In vitro, PFT-? binds both p53 (Kd = 0.82 mM) and Bcl-xL (Kd = 0.80 mM).{19630} PFT-? reduces p53-mediated apoptosis induced by ?-radiation in mouse thymocytes in vitro and protects mice from doses of radiation that cause lethal hematopoietic syndrome. At 25 ?M, PFT-? reduces apoptosis triggered by nutlin-3, which inhibits MDM2/p53 binding and potentiates p53-mediated growth arrest and apoptosis.{19633} PFT-? also interacts selectively with heat shock protein 70 (Hsp70), leading to disruption of the association between Hsp70 and many of its co-chaperones and substrate proteins.{19631}