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- 详细信息
- 文献和实验
- 技术资料
- 保存条件：
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 保质期：
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 英文名：
ML346
- 库存：
现询
- 供应商：
北京索莱宝科技有限公司
- CAS号：
100872-83-1
- 规格：
10mg/2mg/5mg
| 规格： | 10mg | 产品价格： | ￥1640.0 |
|---|---|---|---|
| 规格： | 2mg | 产品价格： | ￥590.0 |
| 规格： | 5mg | 产品价格： | ￥980.0 |
| 基本信息 | |
| CAS | No.100872-83-1 |
| 英文名称 | ML346 |
| 别名 | ;5-(4-Methoxy-trans-cinnamyliden)-barbitursaeure |
| 分子式 | C14H12N2O4 |
| 分子量 | 272.26 |
| 溶解性 | Soluble in DMSO |
| 纯度 | ≥98% |
| 外观(性状) | Solid |
| 储存条件 | Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL | MFCD01177921 |
| SMILES | COC1=CC=C(C=C1)/C=C/C=C2C(=O)NC(=O)NC2=O |
| InChIKey | IXYLVJHFJKDHRM-NSCUHMNNSA-N |
| InChI | InChI=1S/C14H12N2O4/c1-20-10-7-5-9(6-8-10)3-2-4-11-12(17)15-14(19)16-13(11)18/h2-8H，1H3，(H2，15，16，17，18，19)/b3-2+ |
| PubChem CID | 767276 |
| 靶点 | Hsp70;HSF-1 |
| 通路 | Cell Cycle;Metabolic Enzyme&Protease |
| 背景说明 | ML346是 Hsp70 和 HSF-1 的激活剂。ML346 诱导了热休克反应 (HSR) 的基因和蛋白质效应子的特异性增加，包括伴侣蛋白如 Hsp70，Hsp40 和 Hsp27。 |
| 生物活性 | ML346 is an activator of Hsp70 expression and HSF-1 activity， with an EC50 of 4.6 μM for Hsp70. ML346 restores protein folding in conformational disease models， without significant cytotoxicity or lack of specificity. ML346 induces specific increases in genes and protein effectors of the heat shock response (HSR)， including chaperones such as Hsp70， Hsp40， and Hsp27[1]. |
| IC50 | HSP70:4.6μM(EC50;HeLa cells)[1] |
| In Vitro | ML346 is an activator of Hsp70，with an EC50 of 4600 nM in HeLa cells. ML346(10 μM)restores proteostasis，restores CFTR-mediated iodide conductance，and enhances the correct folding of proteins expressed in two different cellular compartments[1]. 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(0.5-25 μM)exhibits cytoprotective effects in cells after a 35 min severe heat shock，and also causes a two-fold protection from H2O2-induced apoptosis[2]. |
| 细胞实验 | ML346 suppress the aggregation of polyQ35 in a C. elegans model，suggesting the probe has efficacy in modifying protein aggregation and associated toxicity[1]. |
| 细胞实验 | HeLa cells are plated at a density of 10，000 cells per well in black 96-well plates in 100 μL 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. 1 μL 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 200 μL of PBS and 200 μL of a solution of 1 μg/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%)[2]. |
| 激酶实验 | In brief，HeLa cells are incubated with either DMSO(negative control)，the positive controls MG132(10 μM)and lactacystin(6 μM)or the PRs A1，A3 and ML346(F1)for 3 and 6 hours and then harvested. Cells are lysed in homogenization buffer(50 mM Tris-HCl，pH7.5，250 mM sucrose，5 mM MgCl2，2 mM ATP，1 mM DTT，0.5 mM EDTA，0.025% digitonin)for 5 min on ice，and total protein concentration of whole cell extract is determined. 3 μg of whole cell extracts are combined with assay buffer(50 mM Tris-HCl，pH 7.5，40 mM KCl，5 mM MgCl2，0.5 mM ATP，1 mM DTT，0.05 mg/mL BSA)in a black 96-well plate and the reaction is initiated by the addition of a 2×(200 μM)fluorogenic peptide substrate Suc-LLVY-AMC. Fluorescence is measured every 10 min using a Synergy H4 multi-mode microplate reader[2]. |
| 数据来源文献 | [1]. Calamini B， et al. ML346: A Novel Modulator of Proteostasis for Protein Conformational Diseases.Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. 2012 Dec 17. [2]. Calamini B， et al. Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol. 2011 Dec 25;8(2):185-96. |
| 单位 | 瓶 |
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