Eprenetapopt (APR-246) 是首创的在TP53突变细胞中恢复野生型p53功能的小分子。Eprenetapopt 引发肿瘤细胞凋亡。Eprenetapopt 还抑制硒蛋白硫氧还蛋白还原酶 1 (TrxR1)。
生物活性 | Eprenetapopt (APR-246) is a first-in-class, small molecule that restores wild-type p53 functions inTP53-mutant cells. Eprenetapopt triggersapoptosisin tumor cells. Eprenetapopt also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance[1][2][3]. |
IC50& Target | p53 activator[1] TrxR1 inhibitor[1] |
体外研究 (In Vitro) | Eprenetapopt inhibits both recombinant TrxR1 in vitro and TrxR1 in cells. Cellular TrxR1 activity is inhibited by Eprenetapopt irrespective of p53 status. Eprenetapopt can directly affect cellular redox status via targeting of TrxR1. Several small molecules have been shown to restore wild-type activity to mutant p53, including CP-31398, PRIMA-1 and Eprenetapopt, MIRA, STIMA, PhiKan-083 and NSC319726. PRIMA-1 and its methylated analog Eprenetapopt promote correct folding of mutant p53, induce cell death by apoptosis, and inhibit tumor growth in mice. Eprenetapopt has also been shown to reactivate mutant forms of the p63 and p73 proteins that share high structural homology with p53[1]. Eprenetapopt is a powerful apoptosis-inducing agent. Eprenetapopt can enhance apoptosis in mutant p53 carrying cells, compared to the p53 null parental cells. Most p53 mutants are in complex with Hsp70 proteins. Eprenetapopt treatment increases Hsp70 expression and nucleolar translocation, in parallel with the induction of nucleolar accumulation of mutant p53. Several lines of evidence suggest that Eprenetapopt can also act independently of the p53 status of the cell. It can radiosensitize prostate carcinoma cell lines with mutant or wild type p53 and p53-/-cells as well. Introduction of mutant p53 (p53ser249 or p53gln248) into p53-/-hepatocarcinoma cells increases sensitivity to Eprenetapopt without the induction of p53 target genes.Eprenetapopt regularly induces apoptosis in mutant p53 expressing cells[2].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 100 mg/mL(501.88 mM;Need ultrasonic) H2O : 50 mg/mL(250.94 mM;Need ultrasonic) 配制储备液 1 mM | 5.0188 mL | 25.0941 mL | 50.1882 mL | 5 mM | 1.0038 mL | 5.0188 mL | 10.0376 mL | 10 mM | 0.5019 mL | 2.5094 mL | 5.0188 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: PBS Solubility: 100 mg/mL (501.88 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (12.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (12.55 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (12.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (12.55 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 4. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (12.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (12.55 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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