Inauhzin is a small molecule that effectively reactivatesp53 by inhibiting SIRT1 activity, and promotes p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress (IC50=3 μM, in A549 cell).
Inauhzin at a concentration of 10 µM elevates p53 levels comparably to actinomycin D at 10 nM and promotes p53-dependent cytotoxicity via its distinct functional groups in human lung carcinoma H460 cells. A lower concentration of Inauhzin (2 µM) enhances both the level and activity of p53, along with initiating p53-dependent apoptosis. It stabilizes p53, prevents its ubiquitylation, and increases p53 acetylation in H460 cells, specifically without affecting tubulin. This acetylation is impacted by the knockdown of SIRT1[1]. At doses up to 2 µM, Inauhzin markedly boosts the expression and activity of p53 in both HCT116p53+/+ and H460 cells in a dose-responsive manner. When combined with Nutlin-3, Inauhzin displays synergistic cytotoxic effects, particularly in cells with low sensitivity to Nutlin-3, and jointly they trigger p53-dependent apoptosis[2].
体内研究
Administered intraperitoneally at 30 mg/kg, Inauhzin significantly initiates apoptosis and reduces tumor growth in H460 xenografts harboring p53[1].
At the same dosage, Inauhzin reduces the tumor volume of HCT116 by about 70%. When used alongside 150 mg/kg Nutlin-3 at 15 mg/kg, Inauhzin shows significant synergy in inducing p53, apoptosis, and tumor suppression in HCT116p53+/+ xenografts[2].
体外研究
Inauhzin at a concentration of 10 µM elevates p53 levels comparably to actinomycin D at 10 nM and promotes p53-dependent cytotoxicity via its distinct functional groups in human lung carcinoma H460 cells. A lower concentration of Inauhzin (2 µM) enhances both the level and activity of p53, along with initiating p53-dependent apoptosis. It stabilizes p53, prevents its ubiquitylation, and increases p53 acetylation in H460 cells, specifically without affecting tubulin. This acetylation is impacted by the knockdown of SIRT1[1].
At doses up to 2 µM, Inauhzin markedly boosts the expression and activity of p53 in both HCT116p53+/+ and H460 cells in a dose-responsive manner. When combined with Nutlin-3, Inauhzin displays synergistic cytotoxic effects, particularly in cells with low sensitivity to Nutlin-3, and jointly they trigger p53-dependent apoptosis[2].
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