ML-346 是 Hsp70 表达和 HSF-1 活性的激活剂，对 Hsp70 的 EC50 为 4.6 μM。 ML-346 在构象疾病模型中恢复蛋白质折叠，没有明显的细胞毒性或缺乏特异性。 ML-346 诱导热休克反应 (HSR) 的基因和蛋白质效应子的特异性增加，包括 Hsp70、Hsp40 和 Hsp27 等伴侣蛋白。
| Cas No. | 100872-83-1 |
| 化学名 | 5-[3-(4-methoxyphenyl)-2-propen-1-ylidene]-2,4,6(1H,3H,5H)-pyrimidinetrione |
| Canonical SMILES | O=C1NC(/C(C(N1)=O)=C/C=C/C2=CC=C(OC)C=C2)=O |
| 分子式 | C14H12N2O4 |
| 分子量 | 272.3 |
| 溶解度 | 0.5mg/mL in ethanol, 30mg/mL in DMSO, or in DMF |
| 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
| Shipping Condition | Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request |
| 产品描述 | ML-346 is an activator of the heat shock response that induces the expression of the heat shock proteins HSP70, HSP40, and HSP27.[1] It induces the expression of the oxidative stress response genes HO1, GCLM, and BiP in mouse embryonic fibroblasts (MEFs) and pretreatment protects cells from severe heat shock-induced death and H2O2-induced apoptosis. It promotes folding of metastable proteins in models of conformational disease, including cellular models of Huntingtin aggregation and cystic fibrosis. It reduces aggregate formation in PC12 cells expressing human Huntingtin exon 1 containing a 74 glutamine expansion when used at a concentration of 10 uM. It also corrects trafficking of cystic fibrosis transmembrane conductance regulator proteins bearing the F508 deletion (F508-CFTR) mutation carried by the majority of cystic fibrosis patients, leading to increased cell surface expression. References
[1]. Calamini, B., Silva, M.C., Madoux, F., et al. Small-molecule proteostasis regulators for protein conformational diseases. Nat. Chem. Biol. 8(2), 185-196 (2011). |
