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17-AAG (KOS953)

现货
Catalog No.
A4054
HSP90抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 700.00
现货
10mg
¥ 600.00
现货
50mg
¥ 1,750.00
现货
100mg
¥ 2,500.00
现货
200mg
¥ 3,500.00
Ship with 10-15 days

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Background

17-AAG is a potent inhibitor of HSP90 with IC50 value of 6 nM in BT474 cells [1].

17-AAG is a synthetic analogue developed from geldanamycin which was found to have significant hepatic toxicity. 17-AAG has an improved toxicity profile and has no hepatic toxicity. 17-AAG can bind to HSP90 and destabilize the client proteins such as HER2, Raf-1, p53 and MAPK signaling. In Multiple myeloma (MM) cells, 17-AAG treatment inhibited cell proliferation and survival. The combination treatment of 17-AAG and bortezomib induced apoptosis in primary MM cells resistant to doxorubicin and bortezomib. The combination of 17-AAG and trastuzumab reduced the expression of ErbB2 in breast cancer cells overexpressing ErbB2. 17-AAG also showed efficacy in thyroid cancer cells and Hodgkin lymphoma cells. Besides that, 17-AAG was found to increased apoptosis in human melanoma xenografts. 17-AAG is now in phase II clinical studies [2].

References:
[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

文献引用

1. 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
2. Jarrett Smith,Geraldine Seydoux, et al. "Liquid-like P granules require ATP hydrolysis to avoid solidification." bioRxiv,Jan. 10, 2018.
3. 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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt585.7
Cas No.75747-14-7
FormulaC31H43N3O8
SynonymsTanespimycin
Solubility≥24.95 mg/mL in DMSO, ≥9.56 mg/mL in EtOH with ultrasonic, <2.34 mg/mL in H2O
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
SDFDownload SDF
Canonical SMILESCC1CC(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

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.

生物活性

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

质量控制和MSDS

批次:

化学结构

17-AAG (KOS953)

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