Tanespimycin

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Chemical Structure| 75747-14-7 同义名 : 17-AAG;NSC 330507;17-AAG, 17 AAG, 17AAG, BAY 57-9352, BAY 579352, BAY579352, KOS-953, KOS-953, KOS-953, Tanespimycin;BMS 722782;KOS 953;CP 127374
CAS号 : 75747-14-7
货号 : A220462
分子式 : C31H43N3O8
纯度 : 98%
分子量 : 585.688
MDL号 : MFCD04973892
存储条件：

Pure form Keep in dark place,Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(85.37 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 HSP90 (heat shock protein 90) is a cellular ubiquitous molecular chaperone responsible for promoting the conformational mutation and stabilization of several client oncoproteins, including Met, B-Raf, p53, Akt, and Kit, function of which is required by tumor cells to maintain appropriate client protein expression necessary for proliferation and survival. 17-AAG is a geldanamycin-derived HSP90 inhibitor with 100-fold higher binding affinity for Hsp90 derived from tumour cells (IC50=6nM, measured by competitive binding assays using a biotinylated GM probe) than normal cells, which may due to the high ATPase activity of tumour Hsp90 by co-chaperones[1]. Exposure to 5μM 17-AAG reduced Bcr-Abl protein levels in HL-60/Bcr-Abl and K562 cells, and also down-regulated the levels of c-Raf in Bcr-Abl-positive cells and the control HL-60/neo cells. Induced cell apoptosis of HL-60/neo, HL-60/Bcr-Abl and K562 cells can be observed after exposure to 5μM 17-AAG for 24-72h[2]. Intraperitoneal injection with 17-AAG at different doses ranging in 5-40mg/kg every other day for three weeks prolonged the survival of mice injected with TGB lymphoma cells. Administration of 40mg/kg 17-AAG effectively impaired the self-renewal of the lymphoma CSCs in vivo[3].
作用机制 1. 17-AAG is a geldanamycin-derived HSP90 inhibitor which can bind to the N-terminal ATP/ADP-binding domain of Hsp90. 2. As tumour cells gradually accumulate mutant and over expressed signalling proteins, this makes HSP90 become engaged in active chaperoning and stabilization of oncoproteins. This will make HSP90 adopt a high affinity form induced by bound co-chaperone proteins and make HSP90 possess higher activity in tumour cells. This can explain why 17-AAG showed higher binding affinity for Hsp90 derived from tumour cells[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
22RV1 Growth Inhibition Assay IC50=3.49168 μM SANGER
23132-87 Growth Inhibition Assay IC50=0.0695 μM SANGER
5637 Growth Inhibition Assay IC50=0.0574 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.71mL

0.34mL

0.17mL

8.54mL

1.71mL

0.85mL

17.07mL

3.41mL

1.71mL
参考文献

[1]Egorin MJ, Zuhowski EG, et al. Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1. Cancer Chemother Pharmacol. 2001 Apr;47(4):291-302.

[2]Weber H, Valbuena JR, et al. Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer. Oncotarget. 2017 Apr 18;8(16):26169-26184.

[3]Yoshida S, Koga F, et al. Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy. Cell Cycle. 2011 Dec 15;10(24):4291-9.