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CAS No. : 309271-94-1
MCE 国际站:Inauhzin
产品活性:Inauhzin 是 SirT1/IMPDH2 的双重抑制剂,同时为 p53 的激活剂,可用于癌症研究。
研究领域:Cell Cycle/DNA Damage | Epigenetics | Apoptosis
作用靶点:Sirtuin | MDM-2/p53
In Vitro: Inauhzin (10 µM) induces p53 levels as effectively as actinomycin D (10 nM), and mediates p53-dependent cytotoxicity through its specific functional groups in human lung carcinoma H460 cells. Inauhzin (2 µM) induces p53 level and activity as well as p53-dependent apoptosis. Inauhzin also stabilizes p53 and inhibits its ubiquitylation. Inauhzin induces acetylation of p53 in H460 cells, but not tubulin, which is affected by knockdown of SIRT1. Inauhzin (0-2 µM) significantly enhances the expression level and activity of p53 in HCT116p53+/+ cells and enhances the expression level and activity of p53 in H460 cells in a dose-dependent manner. Inauhzin and Nutlin-3 demonstrate synergistic cytotoxicity in the Nutlin-3 low-sensitive cells. Inauhzin and Nutlin-3 synergistically induce p53-dependent apoptosis. Inauhzin targets both SirT1 and IMP dehydrogenase 2 (IMPDH2), and acts as a potent p53 activator.
In Vivo: Inauhzin (30 mg/kg, i.p.) effectively induces apoptosis and suppresses tumour growth of H460 xenograft harbouring p53. Inauhzin (30 mg/kg, i.p.) reduces the HCT116 tumor volume by appr 70%. Inauhzin (15 mg/kg) in combination with 150 mg/kg of Nutlin-3 demonstrates a significant synergy on p53 induction, apoptosis and tumor suppression of HCT116p53+/+ xenografts.
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