17-AAG (KOS953)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
17-AAG是一种有效的HSP90抑制剂，在BT474细胞中的IC50值为6 nM[1]。
17-AAG是从geldanamycin发展而来的合成类似物，geldanamycin具有显著的肝毒性，而17-AAG具有改进的毒性特征，没有肝毒性。17-AAG可以与HSP90结合，使客户蛋白去稳定化，如 HER2、Raf-1、p53和MAPK信号。在多发性骨髓瘤（MM）细胞中，17-AAG抑制细胞增殖和存活。17-AAG与bortezomib联合治疗可诱导doxorubicin和bortezomib抗性的原代MM细胞凋亡。17-AAG与trastuzumab联合治疗可减少过表达ErbB2的乳腺癌细胞中ErbB2的表达。17-AAG在状腺癌细胞和霍奇金淋巴瘤细胞中也有效应。除此之外，在人黑色素瘤异种移植模型中，17-AAG增加细胞凋亡。17-AAG目前正处于II期临床研究中[2]。
参考文献：
[1] Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors[J]. Nature, 2003, 425(6956): 407-410.
[2] Dimopoulos M A, Mitsiades C S, Anderson K C, et al. Tanespimycin as antitumor therapy. Clinical Lymphoma Myeloma and Leukemia, 2011, 11(1): 17-22
- 1. Yixuan Wang, Quan Chen, et al. "Lamin-A interacting protein Hsp90 is required for DNA damage repair and chemoresistance of ovarian cancer cells." Cell Death Dis. 2021 Aug 12;12(8):786. PMID:34381017
- 2. Diwei Zheng, Weihai Liu, et al. "AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma." Signal Transduct Target Ther. 2021 Jan 20;6(1):25. PMID:33468990
- 3. Liam Baird, Takafumi Suzuki, et al. "Geldanamycin-derived HSP90 Inhibitors are Synthetic Lethal with NRF2." Mol Cell Biol 2020 Aug 31;MCB.00377-20. PMID:32868290
- 4. Zora Chui-Kuen Chan, Linyan Deng, et al. "Grp94 regulates the recruitment of aneural AChR clusters for the assembly of postsynaptic specializations by modulating ADF/cofilin activity and turnover." eNeuro 3 August 2020, ENEURO.0025-20.2020. PMID:32747457
- 5. Bi Liu, Yunzhu Shen, et al. "Curcumin Derivative C212 Inhibits Hsp90 and Eliminates Both Quiescent and Growing Leukemia Cells." Preprints.org. 17 November 2019.
- 6. 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
- 7. Jarrett Smith,Geraldine Seydoux, et al. "Liquid-like P granules require ATP hydrolysis to avoid solidification." bioRxiv,Jan. 10, 2018.
- 8. Khattar, Vinayak, et al. "Cks1 proteasomal degradation is induced by inhibiting Hsp90-mediated chaperoning in cancer cells." Cancer chemotherapy and pharmacology (2014): 1-10. PMID:25544127
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 585.7 |
| Cas No. | 75747-14-7 |
| Formula | C31H43N3O8 |
| Synonyms | Tanespimycin |
| Solubility | ≥24.95 mg/mL in DMSO; insoluble in H2O; ≥9.56 mg/mL in EtOH with ultrasonic |
| Chemical Name | [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-6-hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-21-(prop-2-enylamino)-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate |
| SDF | Download SDF |
| Canonical SMILES | CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCC=C)C)OC)OC(=O)N)C)C)O)OC |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验 [1]: | |
|
细胞系 |
HT29、HCT116、KM12和HCT15细胞 |
|
溶解方法 |
该化合物在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℃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℃可放置数月 |
|
反应条件 |
IC50：0.2 μM（HT29），0.8 μM（HCT116），0.9 μM（KM12）和46 μM（HCT15），24小时 |
|
实验结果 |
将细胞用一定浓度范围的17-AAG处理24小时，然后在不存在17-AAG的条件下再培养48小时。在四种人结肠腺癌细胞系中，17-AAG显示出抗肿瘤活性，并且剂量依赖性地降低细胞活力。对HT29、HCT116、KM12和HCT15细胞的IC50值分别为0.2、0.8、0.9和46 μM。 |
| 动物实验 [2]: | |
|
动物模型 |
老年nu/nu无胸腺小鼠（具有CWR22异种移植物的雄性和具有CWR22R或CESA6异种移植物的雌性） |
|
剂量 |
腹腔注射，50 mg/kg |
|
实验结果 |
对连续和间歇给药两种方案进行研究。“连续”给药方案为药物给药5天/周，连续3周。 “间歇”方案中，一个5天周期处理小鼠，然后监测肿瘤进展。在进展时，用第二个5天周期的药物处理小鼠。在所有三种异种移植肿瘤模型中，两种方案以剂量依赖性方式延迟生长。使用连续方案，当在对照需要处死的当天进行评估时，50 mg/kg 17-AAG抑制80％的CWRSA6肿瘤生长。在间歇实验中，17-AAG抑制87％的CWRSA6肿瘤生长。在亲代CWR22模型和第二个不依赖雄激素的CWR22R亚系中得到相似的结果。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1] Hostein I, Robertson D, DiStefano F, et al. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Research, 2001, 61(10): 4003-4009. [2] Solit D B, Zheng F F, Drobnjak M, et al. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clinical cancer research, 2002, 8(5): 986-993. |
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| 描述 | 17-AAG (Tanespimycin)是一种有效的HSP90抑制剂，IC50值为5 nM。 | |||||
| 靶点 | HSP90 | |||||
| IC50 | 5 nM | |||||
质量控制和MSDS
- 批次：
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