Pifithrin-α, p-nitro, cyclic (CAS 60477-38-5)

Pifithrin-α, p-Nitro, Cyclic is a cell-permeable p53 inhibitor that exhibits 10-fold higher potency (ED50 = 30 nM in protecting etoposide-induced cortical neuron death) and 50% longer half-life (t1/2 = 6h in neuron culture medium at 37° C) than Pifithrin-α. Pifithrin-α, p-nitro, cyclic behaves p53-dependently but does not block p53 phosphorylation on Ser¹⁵ in reponse to etoposide treatment. Pifithrin-α, p-nitro, cyclic will block p53 posttranscriptional activity, however. Pifithrin-α, p-nitro, cyclic is more stable than the parent compound. Pifithrin-α, p-nitro, cyclic is not active in vivo.

Referenze

1. Komarov, P.G., Komarova, E.A., Kondratov, R.V., et al.A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285(5434), 1733-1737 (1999).
2. Walton, M.I., Wilson, S.C., Hardcastle, I.R., et al.An evaluation of the ability of pifithrin-α and -β to inhibit p53 function in two wild-type p53 human tumor cell lines. Mol. Cancer Ther. 4(9), 1369-1377 (2005).
3. Pietrancosta, N., Moumen, A., Dono, R., et al.Imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: Discovery of a highly potent in vivo inhibitor and its action mechanism. Journal of Medicinal Chemistry 49(12), 3645-3652 (2006).