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17-AAG (KOS953)

Potent inhibitor of chaperone protein Hsp90

17-AAG (KOS953)

Catalog No. A4054
Size Price Stock Qty
Evaluation Sample $28.00 In stock
10mg $60.00 In stock
50mg $175.00 In stock
100mg $315.00 In stock
200mg $515.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Quality Control & MSDS

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Chemical structure

17-AAG (KOS953)

Related Biological Data

17-AAG (KOS953)

Related Biological Data

17-AAG (KOS953)

Biological Activity

Description 17-AAG (Tanespimycin) is a potent inhibitor of HSP90 with IC50 of 5 nM.
Targets HSP90          
IC50 5 nM          

Protocol

Cell experiment: [1]

Cell lines

HT29, HCT116, KM12 and HCT15 cells

Preparation method

Soluble in DMSO to 150 mg/ml. Stock solution can be stored at -80 °C less than 6 months.

Reacting condition

IC50: 0.2 μM (HT29), 0.8 μM (HCT116), 0.9 μM (KM12) and 46 μM (HCT15) 24 hours

Applications

The cells were treated with a range of 17-AAG concentrations for 24 h and then cultured in the absence of 17-AAG for an additional 48 h. 17-AAG showed antitumor activity in these four human colon adenocarcinoma cell lines and reduced cell viabilities dose-dependently. The IC50 values for HT29, HCT116, KM12 and HCT15 cells are 0.2, 0.8, 0.9 and 46 μM, respectively.

Animal experiment: [2]

Animal models

Old nu/nu athymic mice (male with CWR22 xenograft, female with CWR22R or CWRSA6 xenograft)

Dosage form

Intraperitoneal injection, 50 mg/kg

Application

Both continuous and intermittent dosing schedules were studied. The “continuous” dosing schedule involved exposure to drug 5 days/week for 3 consecutive weeks. In the “intermittent” schedule, mice were treated with one 5-day cycle and then monitored for tumor progression. At progression, mice were treated with a second 5-day cycle of drug. Both regimens caused a dose-dependent delay in xenograft tumor growth in all three models. With the continuous schedule, 50 mg/kg 17-AAG caused 80% growth inhibition of CWRSA6 tumor growth when assessed on the day the controls required sacrifice. With the intermittent schedule, 17-AAG caused 87% growth inhibition of CWRSA6 tumor growth. Similar results were noted with the parental CWR22 model and with a second androgen-independent subline CWR22R.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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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Chemical Properties

Cas No. 75747-14-7 SDF Download SDF
Synonyms Tanespimycin
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
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
Formula C31H43N3O8 M.Wt 585.7
Solubility Soluble in DMSO Storage Store at -20°C
Shipping Condition: Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

View Related Products By Research Topics

Research Update

1. Mode of cell death induced by the HSP90 inhibitor 17-AAG (tanespimycin) is dependent on the expression of pro-apoptotic BAX. Oncotarget. 2013 Nov;4(11):1963-75.
Abstract
17-AAG induced BAX-dependent apoptosis at pharmacologically relevant concentrations in BAX knockout HCT116 human colon carcinoma cells both in vitro and in tumor xenografts in vivo, where 17-AAG predominantly inhibited cell proliferation rather than promoting cell death.
4. Combined delivery of paclitaxel and tanespimycin via micellar nanocarriers: pharmacokinetics, efficacy and metabolomic analysis. PLoS One. 2013;8(3):e58619. doi: 10.1371/journal.pone.0058619. Epub 2013 Mar 7.
Abstract
A serious disadvantage in the promising Paclitaxel/17-AAG combination cancer therapy is the requirement of large quantities of toxic organic surfactants and solvents to solubilize the drug.
5. Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation. J Biol Chem. 2013 Jun 14;288(24):17481-94. doi: 10.1074/jbc.M112.439422. Epub 2013 Apr 29.
Abstract
17-AAG induced the down-regulation of AXL expression in a time- and dose-dependent manner through promoting AXL polyubiquitinlation and subsequent proteasomal degradation, in which 17-AAG requires AXL intracellular domain regardless of AXL receptor phosphorylation.

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