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Ganetespib (STA-9090)

现货
Catalog No.
A4385
Hsp90抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 960.00
现货
5mg
¥ 1,260.00
现货
10mg
¥ 1,890.00
现货
50mg
¥ 5,230.00
现货
200mg
¥ 13,300.00
Ship with 10-15 days

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Background

Ganetespib (also known as STA-9090), 5-[2,4-dihydroxy-5-(1 methylethyl)phenyl]-2,4 dihydro-4-(1-methyl-1H indol-5 yl)-3H-1,2,4 triazole-3-one, is a potent small-molecule inhibitor of heat shock protein 90 (Hsp90), which binds to the ATP pocket in the N-terminus of Hsp90 resulting in down-regulation of Hsp90 client protein levels. Being structurally unrelated to geldanamycin-derived Hsp90 inhibitors (17-AAG, 17-DMAG, and IPI-504), ganetespib has a unique triazolone-containing chemical structure and stands out other Hsp90 inhibitors in terms of potency, antitumor activity, and safety profile. Results of previous studies indicate that ganetespib exhibits antitumor activity against a broad range of human cancers, including lung cancer, prostate cancer, colon cancer, breast cancer, melanoma and leukemia.

Reference

Weiwen Ying, Zhenjian Du, Lijun Sun, Kevin P. Foley, David A. Proia, Ronald K. Blackman, Dan Zhou, Takayo Inoue, Noriaki Tatsuta, Jim Sang, Shuxia Ye, Jamie Acquaviva, Luisa Shin Ogawa, Yumiko Wada, James Barsoum, and Keizo Koya. Ganetespib, a unqiue triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 2012; 11: 475-484

Jonathan W Goldman, Robert N Raju, Gregory A Gordon, Iman El-Hariry, Florentina Teofilivivi, Vojo M Vukovic, Robert Bradley, Michael D Karol, Yu Chen, Wei Guo, Takayo Inoue and Lee Rosen. A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies. BMC Cancer 2013; 13:152

文献引用

1. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758
2. Karney-Grobe S, Russo A, et al. "HSP90 is a chaperone for DLK and is required for axon injury signaling." Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9899-E9908. PMID:30275300
3. Khurana N, Kim H, et al. "Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer." Oncol Rep. 2017 Aug 30. PMID:28901514
4. Li QQ, Hao JJ,et al. "Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics." Sci Rep. 2017 Mar 15;7(1):201. PMID:28298630

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt364.4
Cas No.888216-25-9
FormulaC20H20N4O3
SynonymsSTA9090, STA 9090
Solubility≥18.22mg/mL in DMSO, ≥6.4 mg/mL in EtOH with ultrasonic and warming, <2.56 mg/mL in H2O
Chemical Name(5Z)-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-(1-methylindol-5-yl)-1,2,4-triazolidin-3-one
SDFDownload SDF
Canonical SMILESCC(C)C1=CC(=C2NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)C(=O)C=C1O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

NCI-H1975和HCC827细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0.001 ~ 1 μM;5、15或60分钟或24小时

实验结果

在NCI-H1975和HCC827细胞中,使用Ganetespib处理细胞,只需60分钟即可以产生细胞毒性,其IC50值分别为510 nM和800 nM。在NCI-H1975细胞中,使用Ganetespib处理细胞,5分钟足以产生少于1 μM的IC50值。

动物实验 [1]:

动物模型

NCI-H1395非小细胞肺癌异种移植小鼠模型

给药剂量

150 mg/kg;静脉注射;每周1次

实验结果

Ganetespib诱导NCI-H1395肿瘤消退,其T/C值为-49%。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Weiwen Ying, Zhenjian Du, Lijun Sun, Kevin P. Foley, David A. Proia, Ronald K. Blackman, Dan Zhou, Takayo Inoue, Noriaki Tatsuta, Jim Sang, Shuxia Ye, Jamie Acquaviva, Luisa Shin Ogawa, Yumiko Wada, James Barsoum, and Keizo Koya. Ganetespib, a unqiue triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 2012; 11: 475-484.

生物活性

描述 Ganetespib (STA-9090)是HSP90的抑制剂,在OSA 8细胞中的IC50值为4 nM。
靶点 HSP90          
IC50 4 nM          

质量控制

化学结构

Ganetespib (STA-9090)

相关生物数据

Ganetespib (STA-9090)

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Ganetespib (STA-9090)

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Ganetespib (STA-9090)

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Ganetespib (STA-9090)

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Ganetespib (STA-9090)

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Ganetespib (STA-9090)