Tanespimycin (17-AAG)

Catalog No.S1141 Batch:S114102

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Technical Data

Formula

C31H43N3O8
Molecular Weight 585.69 CAS No. 75747-14-7
Solubility (25°C)* In vitro DMSO 117 mg/mL (199.76 mM)
Ethanol 5 mg/mL (8.53 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.
Targets
HSP90 [1]
(Cell-free assay)
5 nM
In vitro 17-AAG, an analog of geldanamycin, exhibits greater than 100 times higher binding affinity for Hsp90 derived from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells with IC50 values of 5-6 nM. [1] 17-AAG causes the degradation of HER2, HER3, Akt, and both mutant and wild-type androgen receptor (AR), leading to the RB-dependent G1 growth arrest of prostate cancer cells such as LNCaP, LAPC-4, DU-145, and PC-3 with IC50 values of 25-45 nM. [2] In addition to inducing apoptosis of Ba/F3 cells transformed with wild-type BCR-ABL with an IC50 of 5.2 μM, 17-AAG has the ability to induce apoptosis of cells transformed with imatinib mesylate-resistant T315I and E255K BCR-ABL mutants with IC50 values of 2.3 μM and 1.0 μM, respectively, by inducing the degradation of both wild-type BCR-ABL protein and mutants. [3]
In vivo 17-AAG displays significantly higher binding affinity for Hsp90 from 3T3-src, B16 or CT26 xenografts in nude mice with IC50 values of 8-35 nM as compared with that from the normal tissues with IC50 values of 200-600 nM. [1] Administration of 17-AAG (~50 mg/kg) causes significant decline in AR, HER2, HER3, and Akt expression in a dose-dependent manner with >50% decline at dose of 50 mg/kg, resulting in the dose-dependent inhibition of androgen-dependent (CWR22) and -independent (CWR22R and CWRSA6) prostate cancer xenografts growth by 67%, 80% and 68% at dose of 50 mg/kg, respectively. [2]
Features Displays very low toxicity toward normal cells.

Protocol (from reference)

Kinase Assay:[1]
  • Hsp90 binding assays

    Purified native Hsp90 protein or cell lysates from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells in lysis buffer (20 mM HEPES, pH 7.3, 1 mM EDTA, 5 mM MgCl2, 100 mM KCl) are incubated with various concentrations of 17-AAG for 30 minutes at 4 °C, and then incubated with biotin-GM linked to BioMag streptavidin magnetic beads for 1 hour at 4 °C. Tubes are placed on a magnetic rack, and the unbound supernatant removed. The magnetic beads are washed three times in lysis buffer and heated for 5 minutes at 95 °C in SDS–PAGE sample buffer. Samples are analysed on SDS protein gels, and western blots done using indicated antibodies. Bands in the western blots are quantified using the Bio-rad Fluor-S MultiImager, and the percentage inhibition of binding of Hsp90 to the biotin-GM is calculated. The IC50 reported is the concentration of 17-AAG needed to cause half-maximal inhibition of binding.
Cell Assay:[1]
  • Cell lines

    BT474, SKBR3, N87, SKOV3, MCF7, MDA468, Hs578T, Hs578Bst, A549, HT29, U87, SKMG3, HT1080, RPTEC, NDF, HMVEC, HMEC, HUVEC, and PBMC cells

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    5 days

  • Method

    Cells are seeded in 96-well plates at 2,000 cells per well in a final culture volume of 100 μL for 24 hours before the addition of increasing concentrations of 17-AAG that is incubated for 5 days. Viable cell number is determined using the Celltiter 96 AQueous Nonradioactive Cell Proliferation Assay. The value of the background absorbance at 490 nm (A490) of wells not containing cells is subtracted. Percentage of viable cells = (A490 of 17-AAG treated sample/A490 untreated cells) × 100. The IC50 is defined as the concentration that gave rise to 50% viable cell number.
Animal Study:[2]
  • Animal Models

    Male nu/nu athymic mice inoculated s.c. with androgen-dependent CWR22 xenograft, and female nu/nu athymic mice inoculated s.c. with androgen-independent xenografts CWR22R and CWRSA6

  • Dosages

    ~50 mg/kg

  • Administration

    Injection i.p.

Customer Product Validation

Data from [Data independently produced by Mol Cancer, 2014, 13, 150]

Data from [Data independently produced by Oncotarget, 2014, 5, 4269-82]

Data from [Mol Cell Biol, 2013, 33(12), 2375-87]

Data from [Age, 2013, 35, 549-62]

Selleck's Tanespimycin (17-AAG) has been cited by 139 publications

Amyloid aggregates induced by the p53-R280T mutation lead to loss of p53 function in nasopharyngeal carcinoma [ Cell Death Dis, 2024, 15(1):35] PubMed: 38212344
RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway [ Oncogenesis, 2024, 13(1):12] PubMed: 38453884
HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer [ Sci Adv, 2024, 10(8):eadk3663] PubMed: 38394204
Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease [ Signal Transduct Target Ther, 2023, 8(1):229] PubMed: 37321990
The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma [ Nat Commun, 2023, 14(1):1516] PubMed: 36934113
FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways [ Mol Cell, 2023, 83(15):2810-2828.e6] PubMed: 37541219
Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis [ J Exp Clin Cancer Res, 2023, 42(1):203] PubMed: 37563605
Steppogenin suppresses tumor growth and sprouting angiogenesis through inhibition of HIF-1α in tumors and DLL4 activity in the endothelium [ Phytomedicine, 2023, 108:154513] PubMed: 36332389
Proteomics Profiling Reveals the Molecular Signatures and Potential Therapeutic Targets of Human Nasopharyngeal Carcinoma [ Mol Cell Proteomics, 2023, 22(6):100567] PubMed: 37172717
Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy [ Int J Mol Sci, 2023, 24(18)13830] PubMed: 37762133

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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