2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
生物活性
Description
In Vivo
In Vitro
化合物的使用
Kinase Assay
Cell Assay
Animal Administration
参考文献
Pifithrin-α is an inhibitor of p53, inhibiting p53-dependent transactivation of p53-responsive genes.
Pifithrin-α (PFTα) was originally thought to be a specific inhibitor of signaling by the tumor suppressor protein p53. Pifithrin-α can protect cells from p53-mediated apoptosis induced by various stimuli and reduce sensitivity of mice to gamma radiation. Pifithrin-α, in addition to p53, can inhibit heat shock and glucocorticoid receptor (GR) signaling, and they suggested that Pifithrin-α targets a factor common to all three signal transduction pathways, such as the hsp90/hsp70-based chaperone machinery. Moreover, it reduces activation of glucocorticoid receptor and rescues mouse thymocytesin vitro and in vivo from apoptotic death after dexamethasone treatment. Pifithrin-α affected both signaling pathways in a p53-independent manner. These observations suggest that Pifithrin-α targets some unknown factor that is common for three major signal transduction pathways. Pifithrin-α has potent antiapoptotic activity (EC50 of 4.16 μM ). Pifithrin-α has a pKa of 9.11 and is an ionic species in physiological medium, whereas the tricyclic derivative has a pKa of 4.36 and exists as the neutral free base at pH 7. The tricyclic derivative is very hydrophobic, with a log P of 4.26. Although Pifithrin-α is generally used at 10?30 μM concentration, the aqueous solubility of its derivative is only 0.2 μM, and it can form a visible precipitate under conditions of typical use. Modification of the carbonyl function creates a stable analogue of Pifithrin-α that remains soluble indefinitely.
