| 名稱 | Tanespimycin |
| 描述 | Tanespimycin (KOS 953) (17-AAG) is an inhibitor of Hsp90 that selectively inhibits BT474 tumor cell Hsp90 (IC50: 5 nM). |
| 細(xì)胞實(shí)驗 | 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]. |
| 激酶實(shí)驗 | 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]. |
| 動物實(shí)驗 | 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]. |
| 體外活性 | 源自腫瘤細(xì)胞的Hsp90與Tanespimycin的結(jié)合親和力是正常細(xì)胞中Hsp90的100倍。體外重組Hsp90伴侶復(fù)合物后，其與Tanespimycin的結(jié)合親和力增強(qiáng)，且ATP酶活性增加[1]。Tanespimycin能促進(jìn)HER2、Akt以及突變型和野生型AR的降解，并導(dǎo)致依賴視網(wǎng)膜母細(xì)胞瘤的G1期生長阻滯在前列腺癌細(xì)胞中[2]。Tanespimycin與Trastuzumab聯(lián)合處理ErbB2過表達(dá)的乳腺癌細(xì)胞系，增強(qiáng)了ErbB2的泛素化、從細(xì)胞表面的下調(diào)及溶酶體降解[3]。 |
| 體內(nèi)活性 | 在非毒性劑量下，Tanespimycin導(dǎo)致前列腺癌異種移植瘤中AR、HER2和Akt表達(dá)水平呈劑量依賴性下降。這種下降速度很快，HER2和AR表達(dá)在4小時內(nèi)分別下降了97%和80% [2]。相比之下，接受了Tanespimycin（5至40 mg/kg）治療的小鼠的脾臟明顯變小，脾臟中滲透的淋巴瘤細(xì)胞減少，轉(zhuǎn)移至其他器官的癌細(xì)胞也顯著降低，與接受車輛對照組治療的小鼠相比。此外，接受Tanespimycin治療的小鼠比僅接受車輛處理的小鼠存活時間顯著延長 [4]。 |
| 存儲條件 | keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 22.5 mg/mL (38.42 mM), Sonication is recommended.
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| 關(guān)鍵字 | tumor | stk38 | Inhibitor | KOS953 | cancer | prostate | HSP | Heat shock proteins | Mitophagy | NSC-330507 | Mitochondrial Autophagy | Tanespimycin | Apoptosis | CP127374 | inhibit | Autophagy | CP-127374 | HER2 | KOS-953 | A549 | NSC330507 | Bacterial | Antibiotic |
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