VER-155008
产品说明书
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同义名 : | - |
| CAS号 : | 1134156-31-2 | |
| 货号 : | A556276 | |
| 分子式 : | C25H23Cl2N7O4 | |
| 纯度 : | 99%+ | |
| 分子量 : | 556.4 | |
| MDL号 : | MFCD18086892 | |
| 存储条件： |
Pure form Keep in dark place, inert atmosphere, 2-8°C In solvent -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : | - | |
| 动物实验配方： |
| 生物活性 | |||
|---|---|---|---|
| 描述 | HSC70 and HSP70 are the two major cytosolic isoforms of the HSP70 family. Between this two proteins, HSP70 is present at relatively low levels in normal cells but can be elevated in expression to protect cells from apoptosis in response to various stressful stimuli such as anticancer agents, especially the HSP90 inhibitors, making it become an important target for anticancer therapy due to its antiapoptotic and oncogenic functions. VER-155008 is a potent inhibitor for Hsp70, Hsc70 and Grp78 with IC50 values of 0.5μM, 2.6 μM and 2.6μM (measured by fluorescence polarisation (FP) assay), respectively. In celluar study, exposure to VER-155008 at 40μM showed a similar response like treatment with HSP90 inhibitor 17-AAG in BT474 or HCT116 cells, like induction of the degradation of HSP90 client protein Her2 and Raf-1, except no induction of HSP70 protein observed. Apoptosis to different extent can be observed in BT474, MDA-MB-468, HCT116 or HT29 cells exposure to VER-155008 at concentration of 0.5μM or 20μM for 24h. Complete colony forming ability of HCT116 or HT29 cells following a 48h-exposure to VER-155008 at concentration>40μM. Combined treatment with VER-155008 at varying concentration to HSP90 inhibitors, 0.5μM VER-82160 or 0.5μM 17-AAG for 24h, could dose-dependently elevate the potency of this two HSP90 to induce cell apoptosis. These suggest that the best use of a small molecule Hsc70/Hsp70 inhibitor, VER-155008, will be in combination with an Hsp90 inhibitor[1]. | ||
| 作用机制 | VER-155008 and bind in the ATPase pocket of Hsp70 and inhibit its intrinsic ATPase activity.[1] | ||
| 细胞研究 | |||||
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| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活性说明 | 数据源 |
| human BT474 cells | Function assay | Binding affinity to Hsp70 nucleotide binding domain in human BT474 cells, IC50=10.4 μM | 20608738 | ||
| human HCT116 cells | Cytotoxic assay | Cytotoxicity against human HCT116 cells by SRB assay, GI50=5 μM | 19256508 | ||
| human HCT116 cells | Function assay | 24 h | Inhibition of HSP70 in human HCT116 cells assessed as reduction of Raf1 protein levels after 24 hrs by Western blot | 19256508 | |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
1.80mL 0.36mL 0.18mL |
8.99mL 1.80mL 0.90mL |
17.97mL 3.59mL 1.80mL |
| 参考文献 |
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