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ML346  ≥98%

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包装规格：5mg 10mg 25mg 50mg 100mg in glass bottle
溶解性：溶于DMSO（12.5mg/mL超声）
产品描述：基本信息 产品编号：M10849 产品名称：ML346 CAS: 100872-83-1   储存条件 粉末 -20℃ 四年     分子式： C14H12N2O4 溶于液体 -80℃ 两年 分子量 272.26 -20℃ 一个月 化学名：  (E)-5-(3-(4-methoxyphenyl)allylidene)pyrimidine-2,4,6(1H,3H,5H)-trione   Solubility (25°C)   体外 DMSO 4mg/mL (14.69mM) Ethanol Insoluble Water Insoluble 体内 现配现用   ＜1mg/ml表示微溶或不溶。 普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 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。   制备储备液   浓度   溶液体积 质量   1mg   5mg   10mg 1mM 3.6730mL 18.3648mL 36.7296mL 5mM 0.7346mL 3.6730mL 7.3459mL 10mM 0.3673mL 1.8365mL 3.6730mL   生物活性 产品描述 一种Hsp70 和 HSF-1 活性的激活剂，针对 Hsp70 的 EC50 为 4.6μM。ML346 恢复构象疾病模型中的蛋白质折叠，而没有明显的细胞毒性或缺乏特异性。 靶点/IC50 HSP70 4.6μM (EC50, HeLa cells)   体外研究 ML346 is an activator of Hsp70, with an EC50 of 4600nM in HeLa cells. ML346 (10μM) restores proteostasis, restores CFTRmediated iodide conductance, and enhances the correct folding of proteins expressed in two different cellular compartments. ML346 (Compound F1) induces multiple responses and strongly induces Hsp70, the oxidative stress response genes (HO1 and GCLM), and a 2.5-fold upregulation of BiP in WT MEF cells. ML346 (0.5-25μM) exhibits cytoprotective effects in cells after a 35 min severe heat shock, and also causes a two-fold protection from H2O2-induced apoptosis. 体内研究 ML346 suppress the aggregation of polyQ35 in a C. elegans model, suggesting the probe has efficacy in modifying protein aggregation and associated toxicity.       推荐实验方法(仅供参考) 激酶实验： Kinase Assay In brief, HeLa cells are incubated with either DMSO (negative control), the positive controls MG132 (10μM) and lactacystin (6μM) or the PRs A1, A3 and ML346 (F1) for 3 and 6 hours and then harvested. Cells are lysed in homogenization buffer (50mM Tris-HCl, pH7.5, 250mM sucrose, 5mM MgCl2, 2mM ATP, 1mM DTT, 0.5mM EDTA, 0.025% digitonin) for 5 min on ice, and total protein concentration of whole cell extract is determined. 3μg of whole cell extracts are combined with assay buffer (50 mM Tris-HCl, pH 7.5, 40mM KCl, 5mM MgCl2, 0.5mM ATP, 1mM DTT, 0.05 mg/mL BSA) in a black 96-well plate and the reaction is initiated by the addition of a 2× (200μM) fluorogenic peptide substrate Suc-LLVY-AMC. Fluorescence is measured every 10 min using a Synergy H4 multi-mode microplate reader.   细胞实验:   Cell Assay HeLa cells are plated at a density of 10,000 cells per well in black 96-well plates in 100μL of DMEM supplemented with 10% FBS and 1% Pen/Strep/Neo. Plates are incubated for 16 hours at 37°C, 5% CO2 and 95% relative humidity before compound addition. 1μL of hit compounds (ML346) in DMSO or DMSO alone are added to the sample or control wells, respectively. Plates are then placed back in the incubator for 24 hours. After incubation, cells are washed 2× with 200μL of PBS and 200μL of a solution of 1μg/mL of calcein AM is added to each well. Cells are then incubated for 45 min at 37°C, 5% CO2 before fluorescence measurement using an Analyst GT multimode reader. Percent cytotoxicity is expressed relative to wells containing cells treated with DMSO only (100%).
保存条件：-20℃

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