| 名称 | Tanespimycin |
| 描述 | Tanespimycin (KOS 953) is an Hsp90 inhibitor (IC50=5 nM) and is selective. Tanespimycin depletes intracellular STK38/NDR1 and decreases STK38 kinase activity. Tanespimycin also downregulated stk38 gene expression. |
| 细胞实验 | Cells were seeded in 96-well plates at 2,000 cells per well in a final culture volume of 100 μl for 24 h before the addition of increasing concentrations of 17-AAG that was incubated for 5 days. Viable cell number was determined using the Celltiter 96 AQueous Nonradioactive Cell Proliferation Assay. The value of the background absorbance at 490 nm (A490) of wells not containing cells was subtracted. Percentage of viable cells ? (A490 of 17-AAG treated sample/A490 untreated cells) × 100. The IC50 was defined as the concentration that gave rise to 50% viable cell number [1]. |
| 激酶实验 | Purified native Hsp90 protein or cell lysates in lysis buffer (20 mM HEPES, pH 7.3, 1 mM EDTA, 5 mM MgCl2, 100 mM KCl) were incubated with or without 17-AAG for 30 min at 4 °C, and then incubated with biotin-GM linked to streptavidin magnetic beads for 1 h at 4 °C. Tubes were placed on a magnetic rack, and the unbound supernatant removed. The magnetic beads were washed three times in lysis buffer and heated for 5 min at 95 °C in SDS–PAGE sample buffer. Samples were analyzed on SDS protein gels, and western blots done using indicated antibodies. Bands in the western blots were quantified, and the percentage inhibition of binding of Hsp90 to the biotin-GM was calculated. The IC50 reported is the concentration of 17-AAG needed to cause half-maximal inhibition of binding. For in vitro reconstitution, 5 μM of purified Hsp90 was combined with 1 μM each of Hsp70, Hsp40, p23, and Hop purified proteins [1]. |
| 动物实验 | B10.BR mice were inoculated with 5×10^5 lymphoma cells through intraperitoneal injection. Seven days following tumor implantation, the mice were I.P. injected with 17-AAG or vehicle (10% DMSO + 40% Cremophor EL: Ethanol (3:1) (v/v) + 50 % PBS) every other day for three weeks. At the cessation of treatment, mice were monitored up to 80 days post tumor cell injection. To determine the effects of 17-AAG on lymphoma initiation in vivo, secondary B10.BR recipient mice were implanted by intraperitoneal injection of 1×10^5 lymphoma cells from the spleens of first-round mice that had been treated with 17-AAG or vehicle. These mice were followed up to 160 days post tumor cell injection to monitor differences in tumor initiation between the mice [4]. |
| 体外活性 | 方法：人A-431、A549、BGC-823、HepG2、HUVEC、L02、MDA-MB-231细胞用Tanespimycin（0-10 μM）处理72小时，使用MTT方法检测细胞生长抑制情况。
结果：Tanespimycin抑制A-431（IC50=89 nM）、A549（IC50=81 nM）、BGC-823（IC50=847 nM）、HepG2（IC50=91 nM）、HUVEC（IC50=282 nM）、L02（IC50=99 nM）、MDA-MB-231（IC50=0.28 μM）细胞生长。[1]
方法： CCA 细胞用Tanespimycin（0.6 μM）处理72小时，使用Western Blot方法检测靶蛋白表达水平。
结果：Tanespimycin下调 Bcl-2、Survivin 和 Cyclin B1，上调 cleaved PARP。[2] |
| 体内活性 | 方法：为研究Tanespimycin的抗肿瘤活性，将Tanespimycin（5-40 mg/kg）每隔一天腹腔注射给接种淋巴瘤小鼠，持续三周。
结果：Tanespimycin在体内抑制淋巴瘤。[3] |
| 存储条件 | keep away from direct sunlight,keep away from moisture,store at low temperature | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1 mg/mL (1.71 mM), Sonication is recommended.
DMSO : 50.5 mg/mL (86.22 mM), Sonication is recommended.
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| 关键字 | tumor | Tanespimycin | stk38 | prostate | NSC-330507 | NSC330507 | Mitophagy | Mitochondrial Autophagy | KOS-953 | KOS953 | Inhibitor | inhibit | HSP90 | HSP | HER2 | Heat shock proteins | CP-127374 | CP127374 | cancer | Bacterial | Autophagy | Apoptosis | Antibiotic | A549 |
| 相关产品 | Aceglutamide | Levulinic acid | Neomycin sulfate | BES | Terbinafine hydrochloride | Hemin | Hydroxychloroquine | Dimethyl sulfoxide | Ethoxyquin | Sodium diacetate | Sulfamethoxazole sodium | D(+)-Raffinose pentahydrate |
| 相关库 | 微生物天然产物库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | 临床失败化合物库 | 高选择性抑制剂库 | 抗衰老化合物库 | 膜蛋白靶向化合物库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |