Pifithrin-α (PFTα)

Описание

Pifithrin-α is an inactivator of p53 that blocks p53-dependent transcriptional activation and apoptosis. It prevents p53-mediated apoptosis induced by cytotoxic compounds in C8 cells at 10 μM and in human umbilical vein endothelial cells at 30 μM. Pifithrin-α can also protect cells from DNA damage-induced apoptosis by a p53-independent mechanism that might involve cyclin D1.

Использование

Pifithrin-α has been used:

• to study the effect of specific p53 inhibitor on p53-upregulated modulator of apoptosis (PUMA) expression after transient global cerebral ischemia (tGCI)
• as p53 inhibitor to treat PA1 cells
• as a tumor protein p53 (TRP53) inhibitor, to treat mouse lung epithelial-12 (MLE-12) cells

Общее описание

A cell-permeable chemical inhibitor of p53. Reversibly inhibits p53-dependent transactivation of p53-responsive genes and reversibly blocks p53-mediated apoptosis. Inhibits p53-dependent growth arrest of human diploid fibroblasts in response to DNA damage but has no effect on p53-deficient fibroblasts. Protects normal tissues from the deleterious side effects of chemotherapy. Has been reported to protect neurons against β-amyloid peptide and glutamate-induced apoptosis.

Биологическая активность

Inhibitor of p53; reversibly blocks p53-dependent transcriptional activation and apoptosis. Protects against neuronal death in models of stroke and neurodegenerative disorders. Active in vivo ; protects mice from the side-effects of cancer therapy associated with p53 induction. Potentially increases reprogramming efficiency of human somatic cells to induced pluripotent stem cells (iPSCs) by silencing p53. Also aryl hydrocarbon receptor (AHR) agonist, causes upregulation of AHR target gene CYP1A1 (EC 50 = 1.1 μ M).